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    ICM case based discussions ICM case based discussions Document Transcript

    • Case Discussions for ICM training Dr PB Sherren ICM and Anaesthetic Specialist trainee 2012
    • ContentsCase 1: Blunt traumatic pericardial rupture and cardiac herniationCase 2: Pulmonary interstitial emphysemaCase 3: Traumatic brain injury and multimodal monitoringCase 4: Acute Traumatic coagulopathy and damage control resuscitationCase 5: Sudden cardiac death andcommotiocordisCase 6: Renal replacement therapy and dosingCase 7: Hyperbaric oxygen therapy in carbon monoxide poisoningCase 8: GuillainBarré Syndrome and immunomodulationCase 9: Extra Corporeal Membrane Oxygenation in Respiratory FailureCase 10: New and novel strategies for managing propranolol overdose
    • Case 1: Blunt traumatic pericardial rupture and cardiacherniationIntroductionCardiac herniation is a significant and potentially fatal complication of blunt traumaticpericardial rupture (BTPR). Despite 60 years of experience, it is an injury thatfrequently results in pre/early hospital death and diagnosis at autopsy, probablyowing to a combination of diagnostic difficulties, lack of familiarity and associatedpolytrauma. Of those who make it to hospital, and are later diagnosed with BTPR,the survival rate is 36.4% - 42.9%.The common issue is that of amissed or delayeddiagnosis. Potentially, with increasing awareness of the injury and improved use andavailability of imaging modalities, survival rates will improve.Clinical problem and relevant managementA 21-year-old male was admitted toa district general hospitalemergency departmentfollowing a high speed motorbike accident. On admission he was resuscitatedaccording to standard ATLS principles. Initially he was noted to have a high alveolar-arterial gradient but was cardiovascularly stable. He was conscious with a GCS of15/15. He was intubated and ventilated due to respiratory distress and high alveolar-arterial gradient. Following intubation, he become progressively morehaemodynamically unstable and was transferred to our trauma centre. By the time ofarrival the patients condition deteriorated; on arrival in our department, he was foundto be on a FiO2 of 1.0 with PaO2 around 10 kPa and requiring high dosenorepinephrine and epinephrine to sustain his mean arterial pressure. He was re-trauma called at this stage and plain radiographs were obtained to further ascertainand clarify his injuries (Figure 1).
    • Figure 1.Plain supine AP chest radiograph showing a prominent, right-sided cardiacsilhouette (boot shaped), bilateral pulmonary contusions, rib fractures, andendotracheal and tube thoracostomies.The finding of dextrocardia had been noted previously at the district general hospitaland was not thought to be pathological at this stage. A further tube thoracostomy didnot improve the hemodynamic status of the patient. The patient was transferred forCT scan where the following images were obtained (Figure 2).Figure 2. Axial chest CT demonstrating multiple parenchymal lungcontusions,collapsed bilateral haemopneumothoraces, tube thoracostomies, surgicalemphysema, large left-sided pneumopericardium, and displacement of the heart intothe right hemithorax.The CT showed a multitude of head and thoracic injuries, as well as a number of ribfractures and bilateral haemopneumothacaces. The presence of pericardial air withherniation of the heart into the right hemithorax was also causing concern. At thisstage the patients condition had not improved and it was agreed to take the patientto theatre to investigate his thoracic injuries. The patient underwent a clamshellthoracotomy where a 10 cm tear in the right of the pericardium was noted with acardiac herniation through the defect. The heart was relocated and the pericardiumrepaired with interrupted non-absorbable sutures.There was an almost immediate reduction in inotrope requirement and the patientwas transferred to ICU. His post-operative care was complicated by a chest infectionand frequent episodes of fast atrial fibrillation secondary to a myocardial contusion,requiring DC cardioversion. He was discharged from ICU after 14 days and made afull recovery.
    • DiscussionCardiac herniation can occur when there is a significant defect within the pericardialsac. Pericardial tears may involve either the superior, left or right pleuropericardium,or the diaphragmatic pericardium[1]. The defect can allow cardiac luxation and, inthe case of diaphragmatic pericardial tear, herniation of abdominal contents into thepericardial sac. Defects of the pleuropericardium usually occur vertically along thephrenic nerve and if the tear is large enough, approaching 8-12 cm, the heart cansublux through the defect[1]. The resulting torsion of the great vessels can lead to aform of obstructive cardiogenic shock and cardiovascular instability[1].As seen with our own experience and that of others, there is often a delay indiagnosis of BTPR and cardiac herniation, which is a real concern given that, oncerecognised, the treatment is simple and effective[2]. Road traffic collisions andsudden decelerations are the most common mechanisms of injury, particularly thoseinvolving a vector of injury from the left side of the chest[1]. The following pattern ofassociated injuries should also arouse suspicion of BTPR[1]: cardiac contusions anddysrhythmias (28%), multiple rib fractures, haemopneumothoraces, pulmonarycontusions, abdominal injuries (27%), pelvic/long bone fractures (49%), spinal cordand traumatic brain injuries (32%).Given the severity of associated injuries, patients usually require invasive ventilationearly on. However, if the patient is conscious, they may report symptoms ofpalpitations, shortness of breath and chest pain as well as angina type pains as aresult of coronary obstruction following herniation[3-5].The main clinical signs, which may be subtle include: Signs similar to that of tamponade; in particular that of hypotension, pulsusparadoxus and raised jugular venous pressure (JVP). This may occur early or late depending on the timing of herniation. This haemodynamic compromise may manifest itself despite fluid administration and inotropic support. Fluctuating haemodynamic parameters, sometimes to the extent of sudden cardiac arrest (often as a result of change in patients position), should evoke a high index of suspicion of BTPR. Tachycardia and dysrhythmias may also be seen, such as the atrial tachyarrhythmias noted in our case. Displaced and heaving apex beat. A splashing murmur "bruit de Moulin" as a result of the heart moving in a haemopneumopericardium.There are a multitude of investigations available to most hospitals that can assist inthe diagnosis including electrocardiogram, chest radiograph, echocardiography,computerised tomography (CT) and magnetic resonance imaging. Along with its
    • increasing availability and use in the multiply injured trauma patients, CT is alsomore sensitive for identifying cardiac axis changes and pericardial discontinuity thanplain radiographs[6,7]. Characteristic changes indicating a pericardial ruptureinclude[6,7]: Focal pericardial dimpling and discontinuity. Pneumopericardium. Interposition of lung between: aorta and pulmonary artery; or heart and diaphragm; or right atrium and right ventricular outflow tract. Characteristic changes for a cardiac herniation include. "Empty pericardial sac" sign, air outlining the empty pleuropericardium as a result of cardiac luxution into the hemithorax. "Collar" sign is the result of compression of the cardiac contour as a result of constriction by the pericardial band caused by the defect. Associated signs include dilated inferior vena cava (IVC), reflux of contrast into IVC and deformed ventricular silhouette, as well as, secondary signs of tamponadeperiportallymphoedema, pericholecystic fluid and ascites.Once BTPR and cardiac herniation has been diagnosed, treatment is simple andeffective. It has even been suggested that, as it is such a rapidly reversible cause ofsudden cardiac arrest, there may be a role for post-arrest emergency thoracotomyfor select patient groups with blunt chest trauma and positional cardiovascularinstability[5]. The treatment of choice for tears of the diaphragmatic pericardium, rightpleuropericardium, and moderate/large left pleuropericardium defects, is surgicalclosure[1,5]. Closure of moderate-sized pericardial defects is best achieved byinterrupted non-absorbable sutures and larger ones with a mesh prosthesis[1].Learning pointsBTPR and cardiac herniation is a complex and often fatal injury that usually presentsunder the umbrella of polytrauma. Patients with blunt chest trauma and any of thefollowing signs are exceptionally high risk for BTPR and the need for an urgentoperative intervention should be considered: Cardiovascular instability with no obvious cause. This instability may be labile and mimic cardiac tamponade, particularly with changes in patient position. A bedside TTE in this setting is a vital tool for exclusion of differential pathology. A prominent, possibly displaced, cardiac silhouette and asymmetrical large volume pneumopericardium. These signs may show varying degrees of prominence on the plain chest radiograph, if there is uncertainty and the patients condition allows, a chest CT should be sought as it has been shown to better delineate the injuries.
    • References 1. Clark DE, Wiles III CS, Lim MK, et al: Traumatic rupture of the pericardium. Surgery 1983: 93; 495-503. 2. JansonJT,Harris DJ, Pretorius J, et al.Pericardial rupture and cardiac herniation after blunt chest trauma Ann ThoracSurg 2003: 75; 581-582 3. Wright MP, Nelson C, Johnson AM, Mcmillan AKR. Herniation of the heart. Thorax 1970: 25; 656-666. 4. Chughtai T,Chiavaras MM, Sharkey P,et al. Pericardial rupture with cardiac herniation. Can J Surg. 2008: 51(5); E101–E102 5. Wall MJ Mattox KL, Wolf DA. The Cardiac Pendulum: Blunt Rupture of the Pericardium with Strangulation of the Heart. The Journal of Trauma Injury, Infection and Critical care. 2005: 59(1); 136-142. 6. Nassiri N, Yu A, Statkus N, et al. Imaging of Cardiac herniation in Traumatic pericardial rupture. Journal of Thoracic Imaging. 2009: Vol 24(1); 69-72. 7. Wielenberg AJ, Demos TC, Luchette FA, et al. Cardiac Herniation Due to Blunt Trauma: Early Diagnosis Facilitated by CT. AJR 2006: 187; W239-W240
    • Case 2: Pulmonary Interstitial Emphysemaand AcuteRespiratory Distress SyndromeIntroductionPulmonary interstitial emphysema (PIE) is a barotrauma-related life-threateningcondition, not uncommon to the neonatologist caring for pre-term babies. For theintensivist, despite being confronted by significant compliance issues resulting fromthe fibroproliferative phase of adult respiratory distress syndrome (ARDS) on a dailybasis, PIE in the critically ill adult is an extremely rare occurrence.Clinical problem and relevant managementAn 87-year-old Caucasian British woman presented to our emergency departmentwith a three-day history of shortness of breath, pyrexia and non-productive cough.Her only significant past medical history was well-controlled hypertension. She wasindependent in her daily activities, did not smoke cigarettes and reported a goodcardiorespiratory reserve prior to the onset of symptoms. The diagnosis ofcommunity-acquired multilobar pneumonia was made with a CURB-65 score ofthree.She was admitted to the high dependency unit with type 1 respiratory failure and ahigh alveolar-arterial oxygen gradient. She received intravenous antibiotics(piperacillin/tazobactam and erythromycin) and non-invasive high-flow continuouspositive airway pressure (CPAP). By the fourth day, the patient had deteriorated,with a chest radiograph showing bilateral alveolar and interstitial infiltrates and a ratioof partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO 2/FiO2) of< 26.6 kPa, which required invasive ventilation. The criteria for ARDS were met andthe cause was thought to be a combination of the direct pneumonic pulmonary injuryand extrapulmonary severe sepsis. With protective lung ventilation, low dosemethylprednisolone, antibiotic therapy and a negative fluid balance, gradualimprovement was made; over the following five days respiratory parameters weanedsufficiently to allow an uncomplicated percutaneous tracheostomy to be performed.On day 10, a period of desaturation required recruitment manoeuvres with aMapleson C circuit that resulted in notable surgical emphysema. The cause wasthought to be a tracheal injury sustained at the time of tracheostomy insertion. Anadjustable flange tube was positioned under bronchscopic guidance just proximal tothe carina in an attempt to limit any further tracking of air through the potentialtracheal defect. Despite these measures, a high alveolar-arterial oxygen gradientand peak airway pressures persisted. A chest radiograph showed more homogenouscentral pulmonary alveolar shadowing. An upper airway bronchoscopy showed noobvious tracheal wall injury and computed tomography (CT) of her chest showedextensive surgical emphysema and a small anterior left sided pneumothorax. Onfurther review of the CT scan, it was felt that the perivascular and peribronchialemphysema was consistent with a diagnosis of pulmonary interstitial emphysema
    • (Figure 1). Over the following days, despite protective ventilatory strategies andintercostal tube thoracostomy, lung compliance along with oxygenation deteriorated.By day 13, the deteriorating respiratory parameters along with inotropic requirementsresulted in a decision to limit therapy and the patient died on day 14. .Figure 1. Axial CT image of the chestdemonstratingclassic findings of trackingperivascular and peribronchial emphysemaDiscussionIn ARDS the inflammatory injury to the lungs begins with an early exudative phasecharacterised by an exaggerated inflammatory response. The alveolar macrophagessecrete cytokines, interleukins and tumour necrosis factor-α, whichinitiatechemotaxis and activate neutrophils. The influx of pro-inflammatory mediatorsresults in the disruption of the alveolar basement membrane and the influx ofproteinaceous fluid into the alveoli spacewithimpairment of surfactant function. If theinflammation is allowed to continue unchecked, a fibroproliferativestage developsand results in type II pneumocyte and fibroblast proliferation with associatedcollagendeposition. The late fibrotic phase of ARDS is categorised byembryonicmesenchymal cell proliferation, neovascularisation and intra-alveolar fibrosis.Acute Lung injury (ALI) and ARDS was first definedand stratified by theAmerican-European Consensus Conference (AECC) in the 1990s. Issues pertaining to thereliability and validity of this definition have arisen since andthis has resulted in arevised Berlin definition being developed 2011.The revised Berlin Definition forARDS was developed in an attempt to address these limitations based on aconsensus process involving a panel of experts [1].
    • Table 1. The differences between the AECC ALI/ARDS and the revised Berlindefinition for ARDS [1].Table 2. The Berlin definition of ARDS [1].
    • Theincidence of PIE in pre-term infants requiring ventilationfor respiratory distresssyndrome to be around19.5%,with a mortality rate of 24% [2]. PIE almost exclusivelyoccurs as a result ofintermittent positive pressure ventilation (IPPV) withpeak airwaypressures exceeding 30 cm H2O [3]. Whenhigh airway pressures and dramaticshearing forces areapplied to a non-compliant lung unit, the result is alveolarductrupture, usually at the terminal bronchiole-alveolarjunction [4]. This allows air toescape into theconnective tissue of the peribronchovascular sheaths,interlobularsepta and visceral pleura, occasionallymigrating into the lymphatic and venouscirculation [4].Pre-term babies are particularlyprone to PIE, because of the high shearing forcesandairway pressures required to re-recruit lung unitswith collapsing pressure exceedingtheir functional residualcapacity, secondary to reduced surfactant levels [4].Otherpostulated risks for PIE include increased amountof pulmonary connective tissue ora sudden reduction inextravascular lung water, which may offer a degreeofprotection against tracking interstitial emphysema.The poorlung compliance associated with ARDS was pivotal in our case, but areductionin extravascular lung water also perhaps had a role toplay in thedevelopment of PIE.Interstitial emphysema has a number of potentiallydetrimentalsequelae [1,5]. These include: compressionatelectasis of adjacent healthy lung andresulting intrapulmonaryshunt which is worsened by recruitmentmanoeuvres;compression of surrounding pulmonary vasculature;and decompression of interstitialblebs intosurrounding spaces, potentially resulting inpneumomediastinum,pneumothorax, pneumopericardium, pneumoperitoneumandsurgical emphysema.Although all the above can be very difficult to managein acritically ill patient, the addition of a pneumothoraxto PIE alone doubles the mortality[1].Chest radiograph findings are often very subtle, andidentification, given the frequentpresence of overlyingdense alveolar shadowing as a result of the lung injuryandexudative processes, make the diagnosis difficult.However, the following findingsmay sometimes be distinguishable[5-7]: parenchymal stippling; lucent mottlingandstreaking extending to the mediastinum; perivascularhalos (from perivascular aircollections); subpleural cysts;lucent bands; and parenchymal cysts or bullae.CT is amore sensitive tool for delineating the pathology,and the classic findings of trackingperivascular andperibronchial emphysema [8] were both demonstratedin our case(Figure 1).The chosen treatment will, to an extent, depend on thedistribution of the diseasealong with the severity andcomplications. The mainstay of treatment is toachieveadequate oxygenation with lower mean and peak airwaypressures, henceminimizing interstitial leak through thedefects [9]. This technique of protective lungventilationand permissive hypercapnia is a familiar one to intensiviststrying to avoidthe many ramifications of volutrauma and barotrauma. There are a number ofothertherapeutic options that may be considered. Lateral decubituspositioning with
    • the affected lung in the dependentposition can be tried as an early conservativeapproach,encouraging plugging of the dependent lung. This is onlyof benefit whenthe disease is localized. Selective mainbronchial intubation and occlusion can beuseful,although only for unilateral disease. High-frequency ventilation(high frequencyjet ventilation or high frequencyoscillatory ventilation) and extracorporealmembraneoxygenation have all been used effectively [1,3-5,9].Beyond these mainstays of treatment, there have beensome case reports and seriesregarding the use of steroidsand surgical resection for persistent localizeddisease,but such therapies have not established a goodevidence base as yet.Learning points The development of PIE is a rare but real risk when caring for patients with ARDS and worsening lung compliance. When undertaking recruitment manoeuvres and interpreting peak airway pressures, it is important to remember the differential lung time constants encountered throughout the diseased lungs. These variations result in an uneven distribution of pressure across the alveoli, and areas of lung with long time constants are at high risk of barotrauma. It is these areas that are at particular risk of developing PIE when exposed to the shearing forces experienced during IPPV.References 1. ARDS Definition Task Force, Ranieri VM, Rubenfeld GD, Thompson BT, et al.Acute respiratory distress syndrome: the Berlin Definition.JAMA. 2012 Jun 20;307(23):2526-33. 2. Greenough A, Dixon AK, Roberton NRC. Pulmonary InterstitialEmphysema. Arch Dis Child 1984, 59(11):1046-1051. 3. Woodring JH. Pulmonary interstitial emphysema in the adult respiratorydistress syndrome. Crit Care Med 1985, 13(10):786-791. 4. Plenat F, Vert P, Didier F, et al. Pulmonary interstitial emphysema. ClinPerinatol1978, 5(2):351-75. 5. Kemper AC, Steinberg KP, Stern EJ. Pulmonary interstitial emphysema: CTfindings. AJR 1999, 172(6):1642. 6. Unger JM, England DM, Bogust JA. Interstitial emphysema in adults:recognition and prognostic implications. J Thorac Imaging 1989,4(1):86-94. 7. Westcott JL, Cole SR. Interstitial pulmonary emphysema in children andadults: roentgenographic features. Radiology 1974, 111(2):367-378.
    • 8. Satoh K, Kobayashi T, Kawase Y, et al. CT appearance of interstitialpulmonary emphysema. J Thorac Imaging 1995, 11(2):153-154.9. Frantz ID, Stark AR, Westhammer J. Improvement in pulmonary interstitial emphysema with high frequency ventilation. Pediatr Res 1981, 15:719.
    • Case 3: Traumatic brain injury and multimodal monitoring.IntroductionTraumatic brain injury remains a common and often debilitating event across theworld, producing significant burdens upon health and social care. Effectiveneurocritical care coupled with timely and appropriate neurosurgical intervention canproduce significant improvements in patient outcome.Clinical problem and relevant managementA 39 year old male was admitted to the Royal London Hospital following an assaultand isolated closed head injury. His initial Glasgow Coma Score (GCS) with the pre-hospital team (HEMS) prior to rapid sequence intubation was 6/15 (E1V2M4). Hehad no lateralising or pupillary signs on initial examinationby the HEMS. On arrival inthe emergency department he had no cardiorespiratory issues on his primary survey.When reassessing his disability on admission it was noted his right pupil wasenlarged (5mm) and unreactive with a normal left pupil. Adequate sedation andanalgesia was achieved with an infusion of propofol 1% and intermittent boluses ofFentanyl. A bolus of 200ml of 20% Mannitol was administered and standardneuroprotective measures were implemented prior to transfer for a CT scan.The CThead showed a large right-sided subdural haematoma with 8mm of midline shift. Hehad an immediate craniotomy and evacuation of haematoma where it was notedtherewas significant underlying parietal contusions. A Licox catheter (IntegraNeurosciences) was placed in the surrounding healthy parenchyma and the patientwas transferred to the ICU. During the initial 48 hours the intracranial pressures(ICP) were extremely labile despite adequate PaO2, PaCO2, cerebral perfusionpressures (CPP), sedation, analgesia and anticonvulsants. A repeat CT scanshowed multiple haemorrhagic contusions with patent basal cisterns but nosurgically amenable lesion. Consideration was given to a hemispheric craniectomybut instead a decision was taken to continue maximal medical management andtarget a PbtO2 of greater than 20mmHg on the Licox whileaccepting higher ICPs.After 5 days the ICP had stabilised and remained stable following a CO2 challenge.The patient was woken and extubated uneventfully. On discharge to theneurosurgical ward he had a GCS of 14/15 (E3V5M6) with no gross neurologicaldeficit. However, he did have a mild cognitive deficit with short term memory issues.DiscussionA sustained elevation in ICP is known to adversely affect patient outcomes[1].Measurement usually requires the presence of an invasive indwelling catheter withinthe subdural space, parenchyma, or ventricular system. However, other none-invasive methods such as near infra-red spectroscopy (NIRS), transcranialdoppler(TCD) and ultrasound (US) assessment of the optic nerve sheath diameter (ONSD)have shown promise as screening tools for extra-axial haematomas[2] and raisedICP[3-5].
    • The importance of ICP (<20-25mmHg) and CPP (60-70mmHg) control and theirincorporation into evidence based guidelines for the management TBI is well-established[6,7]. However, guidelines are designed for a homogenous populationwhich does not translate well to the diversity seen in TBI.The incidence and duration of impaired cerebral pressure autoregulation (CPA) inTBI is variable[8,9]. Peterson et al showed, contrary to the popular belief, that staticCPA was intact in 75.7% of patients with severe TBI[8]. The role of static CPA andperfusion CT scans in the management of severe TBI remains to be elucidated.Dynamic CPA relates to the cerebrovasculature response to transient fluctuations inCPP [10] and can be assessed with pressure reactivity index (PRx)[10], pressurevolume index (PVI)[11] or the use of TCD to assess the mean flow velocity index[12].Uncertainty still remains over the clinical use of CPA and whether there is anassociation between impaired CPA and mortality[13,14]. Johnson et al suggestedthat patients with impaired CPA and lower targeted CPP (<60mmHg) had betteroutcomes[15]. This interesting study, although thought-provoking, was limited by itssmall sample size and that it was a non-randomised controlled study. The future ofindividualised targeting of CPP on the basis of CPA in TBI is continuously evolvingand is now awaiting multicentre randomised control trials.With the use of magnetic resonance or positron emission tomography imaging, it hasbeen identified that significant secondary neuronal injury can occur in the absence ofany pathological changes in ICP or CPP. Hence there is an increasing interest inmultimodal monitoring to identify early markers of secondary cerebral insults. Whenaddressing raised ICP, optimisation of the CBF, cerebral metabolism, CBF-metabolism coupling, immunological and biochemical markers may help mitigate anysecondary cerebral insult. A variety of monitoring devices are commercially availableto assist, including Laser Doppler flowmetry, thermal diffusion flowmetry, NIRS, braintissue oxygen tension (pbtO2), jugular venous oximetry, TCD and cerebralmicrodialysis (MD). In TBI, the use of pbtO2 (LICOX) and MD have proved the mostpromising in recent literature.The brain parenchyma is dependent on a continuous supply of oxygen to maintainaerobic metabolism and cellular integrity. In TBI the oxygen supply and demandvaries dramatically and cerebral hypoxia is common. To measure pbtO2 in vivo, amini Clark electrode can be inserted into the parenchyma. The electrode can beplaced in normal white matter on the side of maximal pathology near the injury, or inthe non-dominant frontal lobe in diffuse injury. The threshold for critical ischemia isusually considered to be 10mmHg [15]. The integration of PbtO2 guided therapiesinto existing CPP/ICP based protocols has been shown to reduce mortality rates andimprove patient outcomes following severe TBI[15]. Spiotta et aldemonstrated thatthe use PbtO2 guided management (PbtO2 >20mmHg) enabled clinicians to toleratehigher ICPs and avoid detrimental side effects of ICP and CPP management [15].While the efficacy of early craniotomy and evacuation of extra-axial bleeds with masseffect is well established, the use of decompressivecraniectomy remains
    • controversial. Decompressivecraniectomy may be performed prophylactically at thetime of removal of mass lesions or as a rescue technique when maximal medicaltherapy has failed; although this reduces ICP [16], as yet no high-quality evidencedemonstrates an improved clinical outcomes.The recent DECRA trial examined the role of early (within 72 hours)decompressivecraniectomy in patients with severe TBI and a refractory intracranialhypertension (greater than 20mmHg) in excess of 15 minutes [17]. In this large,multicentre trial, patients were randomly assigned to either standard care or bifronto-temporo-parietal craniectomy. In keeping with previous literature, patientsundergoing decompression exhibited significantly lower ICPs and reduced ICUlength of stay. However, functional outcome was unfavourable. There are limitationsto the generalisation of these observations. Only 155 patients were recruited over aseven year period from a potential 3478 patients, suggesting a highly specificsample population. It could also be argued that an inclusion threshold of refractoryintracranial hypertension lasting 15 minutes was too short.A number of these concerns may be addressed when the results of theongoingRESCUEicp trial are made available [18]. This randomised controlled studyis evaluating the place of decompressivecraniectomy in the management ofrefractory intracranial hypertension defined as an ICP greater than 25 mmHg for 1 to12 hours at any point following injury. Until then, it appears the role of surgery in themanagement of brain ischaemia is limited to focal lesions.Learning points In TBI there is a variable incidence of impaired CBF autoregulation. Multimodal neurological monitoring and individualised management strategies should be employed in TBI. Individualisation of cerebral perfusion targets against brain-tissue oxygenation parameters and markers of anaerobic metabolism may allow clinicians to accept higher intracranial pressure limits. The evidence base for the use of PbtO2 is growing. In conjunction with traditional monitoring and appropriatetherapeutic interventions, PbtO2 may improve outcomes in TBI. Further trials are required to delineate the role of decompressivecraniectomy in TBI.References 1. Metzger JC, Eastman AL, Pepe PE. Year in review 2008: Critical Care-- trauma. Crit Care. 2009;13(5):226. Epub 2009 Oct 21. 2. Leon-Carrion J, Dominguez-Roldan JM, Leon-Dominguez U, et al. The Infrascanner, a handheld device for screening in situ for the presence of brain haematomas. Brain Injury, September 2010; 24(10): 1193–1201.
    • 3. Rajajee V, Vanaman M, Fletcher JJ, et al. Optic Nerve Ultrasound for the Detection of Raised Intracranial Pressure. Neurocrit Care. 2011 Jul 19. [Epub ahead of print]4. Major R, Girling S, Boyle A. Ultrasound measurement of optic nerve sheath diameter in patients with a clinical suspicion of raised intracranial pressure. Emerg Med J. 2011 Aug;28(8):679-81. Epub 2010 Aug 15.5. Sharma D, Souter MJ, Moore AE, et al. Clinical experience with transcranial Doppler ultrasonography as a confirmatory test for brain death: a retrospective analysis. Neurocrit Care 2010. [Epub ahead of print]6. Farahvar A, Gerber LM, Chiu YL, et al. Response to intracranial hypertension treatment as a predictor of death in patients with severe traumatic brain injury. J Neurosurg. May 2011;114:1471–1478.7. Zeng T, Gao L. Management of patients with severe traumatic brain injury guided by intraventricular intracranial pressure monitoring: a report of 136 cases. Chinese Journal of Traumatology. 2010; 13(3):146-151.8. Peterson E, Chesnut RM. Static autoregulation is intact in majority of patients with severe traumatic brain injury. J Trauma. 2009 Nov;67(5):944-9.9. Sviri GE, Aaslid R,Douville CM, et al. Time course for autoregulation recovery following severe traumatic brain injury. J Neurosurg. 2009 Oct;111(4):695- 700.10. Consonni F, Abate MG, Galli D, et al. Feasibility of a continuous computerized monitoring of cerebral autoregulation in neurointensive care. Neurocrit Care. 2009;10(2):232-40. Epub 2008 Oct 16.11. Lavinio A, Rasulo FA, DePeri E, et al. The relationship between the intracranial pressure–volume index and cerebral autoregulation. Intensive Care Med 2009; 35:546–54912. Sorrentino E, Budohoski KP, Kasprowicz M, et al. Critical thresholds for transcranialdoppler indices of cerebral autoregulation in traumatic brain injury. Neurocrit Care. 2011 Apr;14(2):188-93.13. Zweifel C, Lavinio A, Steiner LA, et al. Continuous monitoring of cerebrovascular pressure reactivity in patients with head injury. Neurosurg Focus. 2008;25(4):E2.14. Johnson U, Nilsson P, Ronne-Engstro E, et al. Favorable Outcome in Traumatic Brain Injury Patients With Impaired Cerebral Pressure Autoregulation When Treated at Low Cerebral Perfusion Pressure Levels. Neurosurgery. 2011 Mar;68(3):714-21; discussion 721-2.15. Spiotta AM, Stiefel, MF, Gracias VH, et al. Brain tissue oxygen–directed management and outcome in patients with severe traumatic brain injury.J NeurosurgSep 2010;113:571–580.
    • 16. Taylor A, Butt W, Rosenfeld J, et al. A randomized trial of very early decompressivecraniectomy in children with traumatic brain injury and sustained intracranial hypertension. Childs Nervous System. 2001 Feb. 23;17(3):154–162.17. Cooper DJ, Rosenfeld JV, Murray L, et al. DecompressiveCraniectomy in Diffuse Traumatic Brain Injury. N Engl J Med. 2011 Apr. 21;364(16):1493– 1502.18. Hutchinson PJ, Menon DK, Kirkpatrick PJ. Decompressivecraniectomy in traumatic brain injury - time for randomised trials? ActaNeurochir. 2004 Nov. 2;147(1):1–3.
    • Case 4: Acute traumatic coagulopathy and damage controlresuscitationIntroductionUncontrolled haemorrhageis the most common cause of potentially preventabledeath in trauma patients. The aetiology of trauma induced coagulopathy iscomplicated but awareness and timely intervention with damage control resuscitationcould help improve patient outcomes.Clinical problem and relevant managementA 40 year old male was admitted to our trauma centre following a high speed motorbike collision. The physician-staffed helicopter emergency medical service (HEMS)attended the patient initially. The injuries noted by HEMS on arrival included a rightcomplete traumatic forequarter amputation with significant exsanguination, rightpneumothorax, pelvic injury and closed head injury with a GCS 7/15 (E1V2M4). Thepatient was in cardiorespiratory extremis and required an emergent rapid sequenceinduction, right open thoracostomy, direct wound compression, sam pelvic sling, 1gof tranexamic acid, 250ml 7.5% saline and 500ml of hartmans solution to maintainradial pulses. Despite these interventions there were persistent volume issues and amassive transfusion pre-alert was ordered. The primary survey on arrival in thetrauma centre showed a stable airway and breathing system, but despite on-goinghaemostatic resuscitation with a Level 1 rapid transfusor, the haemodynamicinstability persisted with a severe lactic acidaemia (pH 6.8 and lactate 16) andnegative E-FAST scan. Other investigations of note on arrival in the ED included anINR and APTTR of 2.6 and 2.1 respectively. Given the ongoing transfusionrequirements and haemodynamic instability the patient went straight to theatres forsurgical haemostasis. During the damage control surgery a massive transfusion wasrequired targeting systolic blood pressure of approximately 80mmHg. A helical CTscan from the head through to pelvis was undertaken prior to transfer to the ICU. Onarrival in the ICU the patient had received : 23 units of packed red blood cells, 16 units of fresh frozen plasma, 3 pooled units of platelets and cryoprecipitate, 2g tranexamic acid, 3g Calcium chloride, 2000ml compound sodium lactate
    • Figure 1. Chest radiograph as part of the primary survey.DiscussionHypothermia, acidaemia and coagulopathy or the „lethal triad‟, is a well describedentity in the trauma population and is associated with significant mortality [1].Atraumatic insult, coupled with systemic hypoperfusion results in a decreased oxygendelivery, a shift to anaerobicmetabolism, lactate production and metabolicacidaemia. Common instigators of hypothermia in trauma include exposure, massivecold fluid resuscitation and impaired endogenous heat production as a result ofanaerobic metabolism.Traditionally the aetiology of a trauma induced coagulopathywas thought to be multifactorial and involve the lethal triad, dilutional coagulopathy,pre-existing bleeding diathesis and disseminated intravascular coagulation (Figure2).
    • Figure 2. A diagram showing some of the mechanisms leading to coagulopathy in theinjured.Interestingly in the case described here, a significant early coagulopathy was evidenton arrival in the ED despite a short pre-hospital time, minimal fluid resuscitation andnormothermia. In 2003,Brohi et al showed that around 25% of severely injuredtrauma patients present to hospital with a significant coagulopathy which is unrelatedto fluid administration [2,3]. The early coagulopathy has become known as the AcuteTraumatic coagulopathy (ATC) or Acute Coagulopathy of Trauma Shock (ACoTS). Itis associated with an increase in transfusion requirements, injury severity scores,organ dysfunction and mortality rates [2-5].ATC is an impairment of haemostasis involving a dynamic interaction betweenendogenous anticoagulants and fibrinolysis that is initiated immediately after aninjury [5]. ATC is driven by an endothelial injury and hypoperfusion, which results inin increased thrombomodulin expression and activation of protein C (Figure 3). Theinhibitory effect of activated protein C on clotting factors V/VIII and plasminogenactivator inhibitor-1 (PAI-1)would appear key in the development of ATC [5,6].
    • Figure 3. Expression of thrombomodulin following a traumatic injury results inincreased activation of protein C with resulting impairment of clotting factors V/VIIIand reduction in thrombin generation. Activated Protein C also has an inhibitoryeffect on PAI-1 which results in unregulated tPA activity and fibrinolysis.Damage control resuscitation (DCR) describes a package of care for thehaemorrhaging trauma patient. It involves early damage control surgery, haemostaticresuscitation and permissive hypotension. DCR aims to control haemorrhage earlywhile aggressively targeting the ATC and lethal triad. DCR has emerged as theaccepted standard of care and some observational studies have suggested asurvival benefit [6].The priority for any haemorrhaging trauma patient is good haemostasis. Unstablepatients with major trauma do not tolerate prolonged definitive surgery and hence theemergence of damage control surgery. The aim of damage control surgery is tonormalise physiology at the expense of anatomy. The priorities are: • Stop haemorrhage (Packing, clamping, resection +/- interventional radiology) • Minimise contamination • Limb saving procedures • Good wash out of cavities • Drains and low threshold for Laparostomy • Definitive surgery another dayHaemostatic resuscitation describes the aggressive early use of packed red bloodcells, clotting products and coagulation adjuncts in an attempt to mitigate the effectsof the ATC and lethal triad in major trauma patients. The exactPRBC:FFP ratioremainsunclear, but should ideally be less than 2:1 [7].In massive transfusions alongwith appropriate FFP, platelet and fibrinogen supplementation, consideration shouldbe given to early adjunctive therapiessuch as tranexamic acid [8] while maintainingionised calcium levels greater than 1.0 mmol/L [9].
    • Permissive hypotension involves titrated volume resuscitation, which targets asubnormal end point that maintains organ viability until haemorrhage is controlled.By avoiding overzealous fluid resuscitation which targets normotension, the hope isto preserve the first and often best clot. Although permissive hypotension isfrequently employed in traumatic haemorrhage, there is really only robust evidencethat it is advantageous in penetrating trauma [10]. In blunt trauma there is a relativepaucity of good evidence to guide practice, while strong evidenceexists formaintaining cerebral perfusion pressures when there are associated headinjuries.The end points for resuscitation will depend on age, premorbidautoregulatory state and acute pathology. „Rule of thumb‟ resuscitation end pointsinclude: Penetrating trauma - maintain cerebration or central pulse or SBP~60mmHg Blunt trauma – maintain radial pulse or SBP >80mmHg Head injury – maintain temporal pulse or SBP >100mmHg Spinal cord injury – Spinal cord perfusion can be improved with SBP>90mmHg, but no functional outcome data as yet.DCR is an ever evolving concept, and potential future strategies that are as yetunproven include: Increasing use of thromboelastometry (TEG/ROTEM) to guide haemostatic resuscitation. Prothrombin complex concentrate (FII, VII, IX and X) in non-warfarin patients Fibrinogen complex concentrate (fibrinogen and FXIII) over cryoprecipitate. Alkalising agents such asTris-hydroxymethylaminomethane (THAM) in massive transfusion with severe acidaemia. Novel hybrid resuscitation strategies. High flow/low pressure resuscitation – endothelial resuscitation and microvascular washout. Suspended Animation. Platelet functional assessment using platelet mapping and aggregometryvs traditional PF-100.Learning points Early coagulation dysfunction is common in trauma patients with haemorrhagic shock. Tailored management of the „lethal triad‟ and ATC is essential. DCR is an emerging standard of care, however, some of its components are pushing the boundaries of what is good evidence based medicine.References
    • 1. Moore EE. Staged laparotomy for the hypothermia, acidosis, and coagulopathy. Am J Surg 1996;172:405-410.2. Brohi K, Singh J, Heron M, et al. Acute Traumatic coagulopathy. J Trauma. 2003;54:1127-1130.3. Davenport R, Manson J, De‟Arth H, et al. Functional definition and characterization of acute traumatic coagulopathy. Crit Care Med. 2011;39(12):2652-2658.4. Maegele M, Lefering R, Yucei N, et al.Polytrauma of the German Trauma Society (DGU). Early coagulopathy in multiple injury: an analysis from the German Trauma Registry on 8724 patients. Injury. 2007 Mar;38(3):298-304.5. Firth D, Davenport R, Brohi K. Acute traumatic coagulopathy. CurrOpinAnaesthesiol. 2012 Apr;25(2):229-34.6. Cotton BA, Reddy N, Hatch QM, et al.Damage control resuscitation is associated with a reduction in resuscitation volumes and improvement in survival in 390 damage control laparotomy patients. Ann Surg. 2011 Oct;254(4):598-605.7. Davenport R, Curry N, Manson J, et al.Hemostatic effects of fresh frozen plasma may be maximal at red cell ratios of 1:2. J Trauma. 2011 Jan;70(1):90-5; discussion 95-6.8. CRASH-2 collaborators, Roberts I, Shakur H, Afolabi A, et al.The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial. Lancet. 2011 Mar 26;377(9771):1096-101, 1101.e1-2.9. Dawes R, Thomas GO. Battlefield resuscitation.CurrOpinCrit Care. 2009 Dec;15(6):527-3510. Bickell WH, Wall MJ Jr, Pepe PE, et al.Immediate versus delayed fluid resuscitation for hypotensive patients with penetrating torso injuries. N Engl J Med. 1994 Oct 27;331(17):1105-9.
    • Case 5: Sudden cardiac death and commotiocordisIntroductionSudden cardiac death in adolescents and young athletes is a rare occurrence with alarge number of differential diagnoses. Early recognition and management isessential to a successful resuscitation and outcome.Clinical problem and relevant managementA 19 year old gentleman with no previous medical history was brought by ambulanceto the Emergency Department resuscitation room following an impact to the centralchest in a heavy rugby tackle.According to bystanders, he was knocked backwards, sustaining a low impact injuryto the occiput, and was unconscious from this point. Paramedics arrived at the sceneand three-point immobilisation of the cervical spine was instituted. His airway was ofconcern due to his GCS of 4/15, therefore an oropharyngeal airway was inserted.There was good air entry throughout both lung fields. He was hypotensive with ablood pressure of 64/35 and had a heart rate of 35. ECG monitoring revealedcomplete heart block. En route to hospital, his rhythm degenerated to ventricularfibrillation, and CPR was started. His rhythm defibrillated to sinus rhythm after onebiphasic shock given at 200J, and he began to regain consciousness.On arrival to hospital, both cardiac arrest and trauma teams were in attendance. Atthat point, his GCS had increased to 6/15 and he was intubated. Lung fieldsremained clear and he was cardiovascularly stable with a blood pressure of 135/86,a heart rate of 98 and an ECG showing normal sinus rhythm. Blood glucose levelwas 7.4mmol/L. Chest and pelvic radiographs did not reveal an abnormality, and afastscan was negative. After completion of the primary survey, he was transferred tothe CT scanner for a CT of the head, neck, chest, abdomen and pelvis, and wassubsequently transferred to ICU, where he remained ventilated.The following day, he was extubatedand a secondary survey was performed with noinjuries found. He was stepped down to CCU for cardiac monitoring and had nosignificant elevation in his cardiac enzymes.In hospital he underwent an echocardiogram revealing a structurally normal heartwith normal LV function and negative electrophysiological investigations. On balanceit was felt given the minimal trauma,negative investigations and rapid improvementfollowing defibrillation this represented a case of commotiocordis.He was subsequently discharged from hospital with no cardiological or neurologicalsequelae.DiscussionThere are a number of differential diagnoses in this clinical scenario, which shouldinclude causes of sudden cardiac death (SCD) in young athletes. SCD in young
    • athletes has an estimated incidence of 1-3/100 000 person years [1]. The risk inmales is approximately nine times higher than that in females [1].Commotiocordis, a disruption to the cardiac rhythm, occurring from a direct impact tothe anterior chest wall, although rare, is high in the list of differentials for this patient[2].The energy transmitted to the myocardiumalters ventricular dissipation duringrepolarisation and triggers ventricular depolarisation, which could result in re-entryand ventricular fibrillation (Figure 1).The phenomenonusually causes ventricularfibrillation in patients with structurally normal hearts even after only a modest force[2,3]. In an experimental model, a single impact over the heart, timed at 10-30ms atthe vulnerable point of the repolarisation before the T-wave peak can induceventricular fibrillation [4]. This is the same principle that governs electricalcardioversion of tachyarrhythmias,and why the direct current must be synchronisedto the R wave to avoid inadvertent conversion to ventricular fibrillation via the „R onT‟ phenomena. Shortening of the cardiac cycle due to tachycardia during exercisemay render the heart more susceptible to this phenomenon. It is thought that a blowof 50J is low enough to induce cardiac arrest, and many sporting injuries involveinjuries of much higher energy.Figure 1. Variables and mechanism involved in the development of commotiocordis[8].Around 10-20 cases are added to the CommotioCordis Registry per year. It is mostcommon in adolescence but is also seen in older individuals. It must be differentiated
    • from contusiocordis, a condition of blunt cardiac trauma causing structural cardiacdamage,such asmyocardial contusions [5].The majority of those affected by commotiocordis die unless defibrillated within threeminutes [6]. It was fortunate in this case that the patient‟s initial rhythm was completeheart block, a rhythm that has been described previously in this setting clinically andexperimentally, and that his subsequent cardiac arrest was witnessed and actedupon quickly during transfer [4,7]. The increasing prevalence of automated externaldefibrillators, particularly at large scale sporting events may help to prevent deathsdue to this condition.Alternate causes of sudden cardiac death should be sought and aggressivelyexcluded prior to a diagnosis of commotiocordis being made.Alternate causes ofSCD could include undiagnosed coronary artery disease, cardiomyopathies,myocarditis, congenital coronary/aortic anomalies and ion channelopathies includingBrugada syndrome. Cross et al published a comprehensive review on suddencardiac death in adolescents in 2011 [8]. The table below details the incidence of thevarious aetiologies (Table 1).
    • Table 1. Underlying heart disease of sudden cardiac death in various studies [8].
    • The use of implantable cardioverter-defibrillators is controversial in survivors ofsuspected commotiocordis as it is unlikely to occur twice, but may be prudent if theexact cause of cardiac arrhythmia is uncertain. A low threshold could be wise whenyou consider a certain number of channelopathies are difficult to diagnose and theremay be many variants still to be discovered.Prevention of blunt chest trauma with chest protectors is controversial, as somebelieve that it does not dissipate the energy inflicted in cases of commotiocordis.Newer forms of chest protection are under trial [9]. Educating athletes in avoidanceof direct chest wall trauma may also help in the prevention of this condition occurringprimarily.Learning points There are a large number of potential causes of SCD in young healthy individuals. Commotiocordis and resulting ventricular fibrillation is an extremely rare occurrence that requires immediate defibrillation to maximise the potential for a positive outcome.References 1. Borjesson M, Pelliccia A. Incidence and aetiology of sudden cardiac death in young athletes: an international perspective.Br J Sports Med.2009 Sep;43(9):644-8. 2. Maron BJ, Gohman TE, Kyle SB, et al. Clinical profile and spectrum of commotion cordis. JAMA 2002;287:1142–6. 3. Maron BJ, Poliac LC, Kaplan JA, et al. Blunt impact to the chest leading to sudden death from cardiac arrest during sports activities. N Engl J Med 1995;333:337–42. 4. Link MS, Wang PJ, Pandian NG, et al. An experimental model of sudden death due to low-energy chest-wall impact (commotiocordis). N Engl J Med 1998;338:1805–11. 5. Commotiocordis: ventricular fibrillation triggered by chest impact-induced abnormalities in repolarization. CircArrhythmElectrophysiol. 2012;5(2):425-32. 6. Maron BJ, Ahluwalia A, Haas TS, et al. Global epidemiology and demographics of commotiocordis.Heart Rhythm. 2011;8(12):1969-71. Epub 2011 Jul 18. 7. Thakar S, Chandra P, Pednekar M, et al.Complete heart block following a blow on the chest by a soccer ball: a rare manifestation of commotiocordis.Ann NoninvasiveElectrocardiol. 2012;17(3):280-2. 8. Cross BJ, Estes NA 3rd, Link MS.Sudden cardiac death in young athletes and nonathletes. CurrOpinCrit Care. 2011 Aug;17(4):328-34.
    • 9. Maron BJ, Estes NA 3rd. "Medical Progress: Commotio cordis". N Engl J Med 2010; 362 (10): 917–27.
    • Case 6:Renal replacement therapy and dosingIntroductionRenal replacement therapy (RRT) is the artificial extracorporeal or intracorporealblood purification when intrinsic renal homeostasis is impaired or lost. This type oforgan support is often over simplified on the ICU despite a complexity thatexceedsventilatory support. The fact acute kidney injury (AKI)is still associated withhigh mortality ratescould lead us to hypothesise there is still room for improvementon current practice [1].Clinical problem and relevant managementA 58 year old gentleman, with no significant past medical history, was admitted witha severe community acquired pneumonia secondary to a streptococcal pneumonia(CURB-65 score 4/5). He presented with a direct pulmonary severe ARDS(PaO2/FiO2 <100mHg with PEEP>5cmH2O), septic shock and MODS. He wasventilated with protective lung ventilator strategies but despite high PEEP, reverseI:E ratios and permissive hypercapnea,he deteriorated and required a trial of highfrequency oscillatory ventilation. His intravascular volume was augmented with theappropriate use of fluid resuscitation, which was guided by a LiDCO and optimisationof stroke volume responsiveness and SVV/PPV. He was started on norepinephrine,L-argipressin (0,04u/min) and dobutamine to maintain a mean arterial pressuregreater than 65mmHg.In spite of his improved oxygen delivery and aggressive antimicrobial therapy heremained profoundly acidaemic. The origin of his metabolic acidaemia was thoughtto be overwhelming sepsis withmicrovasculardyfunction and a lactic acidaemia (TypeB1) mixed with an AKI and uraemicacidaemia, His AKI was thought to be as a resultof pre-renal hypoperfusion and intra-renal microvascular dysfunction as a result ofhis sepsis. The end result was that of an ischaemic acute tubular necrosis (ATN).Early continuous venovenoushaemofiltration(CvvHF) was instigated to improve themetabolic status. In addition to improving his metabolic status, it was hoped CvvHFwould help gain some control over his significant inflammatory humoral response,vasoplegic shock and allow optimisation of his fluid balance/extravascular lungwater. Much discussion was had over the best renal replacement therapy modality toutilise and the possible benefit of high intensity renal dosing.By day 3 of the ICU admission the patient deteriorated and became vasopressorunresponsive and developed disseminated intravascular coagulation (DIC). Multiplerenal replacement filters suffered from premature coagulation dysfunction despiteincreased pre-filter dilution and various anticoagulants. The patient succumbed to hispneumococcal sepsis on day 4 of their ICU admission.
    • DiscussionCurrently there is a great deal of debate and variations in practice when it comes toappropriate RRT mode, dose and timing of initiation [2].There are a multitude ofindications for initiating RRT, some with more robust evidence than others. Aconsensus statement issued by the Acute Dialysis Quality Initiative (www.adqi.org) in2001 listed some absolute indications based on expert opinions and best practice: Absolute renal indications:  Symptomatic Uraemia (encephalopathy, pericarditis and bleeding)  Nephrogenic Pulmonary Oedema  Severe unresponsive hyperkalaemia (>6 mmol/L and/or ECG abnormalities.  Severe metabolic academia (pH<7.15)  Urine output less than 200ml/24 hours  Extreme creatinine and urea  Relativenon-renal indications:  SIRS/sepsis  Fluid balance  Rhabdomyolsis  Overdose/Drug accumulation (Haemoperfusion)  Renal protection pre/post contrast, againstcontrast- inducednephropathy  Temperature control  Plasmapheresis/Exchange (immune complexes)  Mg at least 4 mmol/l and/or anuria/absent deep tendon reflexes.  Severe acute liver failure with molecular adsorbent re-circulating system (MARS, PROMETHEUS) as bridge to transplantOnce the decision to initiate RRT has been undertaken, the first decision to be madeis on the mode of RRT and whether that should be delivered intermittently orcontinuously: Intermittent RRT  HD most commonly (IHD)  Peritoneal dialysis  CRRT  SCUF - Slow Continuous Ultrafiltration  Ultrafiltration - fluid removal  CvvHF- Continuous Veno-Venous Hemofiltration  Convection - Small, medium and some large size molecules MW <30000 Daltons  CvvHD- Continuous Veno-Venous Hemodialysis  Diffusion - Small molecules <500 Daltons
    •  CvvHDF- Continuous Veno-Venous Hemodiafiltration  Diffusion and Convection- small and medium sized molecules  Niche techniques  Plasmapheresis/exchange  HaemoperfusionCRRT is intended to substitute for impaired renal function over an extended period oftime and applied for 24 hours a day.Patients with acute kidney injury as part of amulti-organ dysfunction syndrome(MODS) are less likely to tolerate fluid shifts,cardiovascular instability and any further secondary renal insult. Correspondingly inpatients with MODS, CRRT is certainly better tolerated in patients withhaemodynamic instability and raised intra cranial pressure [3-5]. A great deal ofequipoise currently exists on the ideal timing andmode of RRT for critically illpatients, with a lack of mortalitybenefit of CRRT over IHD [6,7]. It is important torealise that lack of coarse outcome data doesn‟t mean that good individualised RRTdoesn‟t have a role or tangible impact on an individual‟s ICU course. As suchphysicians should endeavour to time and utilise the appropriate RRT for patientsbasedon underlying pathology, haemodynamic status, fluid balance, biochemicalderangement, acid-base disturbance and local resource availability and protocols.RRT dose is the term for the amount ofdialysis required in order to achieve a certainlevel of blood purification.It is commonly measured in either ml/kg/hour in continuousRRT versus urea filtration fraction or clearance in IHD. Appropriate dosing of RRT inthe critically ill depends upon the patient‟s clinical status (starting point of solute to becleared and degree of metabolic imbalance), themolecular weight of the solute to becleared (Figure 1), and the target level for the desired solute.Figure 1. Molecular weights of various solutes relevant to RRT.
    • The dose of RRT is dependent on timing schedule, modality,membrane type,extracorporeal blood flow and dialysis/replacement flow. RRT dose can be assessedby direct measurement of effluent fluid solute content; however, it is easily estimatedin CRRT because of a few simple assumptions. In CvHF small solute clearanceisconsidered equal to the ultrafiltration rate. Increasing the pre-membrane dilutionwill increase the filtrate formation but reduces the diffusion gradient and hence soluteclearance. During CvvHDF the urea concentration in the dialysate will equilibratewith that in the plasma, andclearance can be approximated by the dialysate flowrate. When calculating the total renal dose in CvvHDF, it is important to include theultrafiltration rate to the dialysate rate. The above approximationshave been shownto acceptably correlate with a more formal set of measurements of urea clearance[8].Ten years ago Ronco et al published one of the first randomised control trials tosuggest high intensity or augmented dose RRT(35 vs 20ml/kg/hr) had a mortalitybenefit in the critically ill [9].However, two landmark multicentre randomised controltrials in America (ATN study) and Australasia (RENAL study) showed that a highrenal dosing regime in RRT conferred no mortality benefit [7,10]. The RENALstudycompared 25 to 40 ml/kg/hrCvvHDF, while the ATN study compared 20ml/kg/hrCvvHDF or three IHD per week to 35 ml/kg/hr CVVHDF or daily IHD. Thesemethodologically sound RCTs have certainly answered the question regarding thebenefit of high intensity of RRT for the general ICU population.However, as with all multicentre RCTs one must always exercise caution beforeapplying to individual units and the heterogeneous ICU population. The first thing toconsider when talking about renal dosing is the discrepancy often seen between theintended prescribed renal dose and the actual delivered dose. In an audit completedat The Royal London ICU, we prospectively observed 59 patients requiring RRT witha totalof 365 filters uses between July 2010 and January 2011. Fifty-nine filters werepurposefully discontinued, leaving 306 filters that unexpectedly failed due to earlycoagulation or access issues. The mean filter lifespan was 21.21 hours (SD 18.96)and the mean timetaken for filter changes was 3.05 hours (SD 1.24).These results are by no means unusual and are comparable to previously publishedwork by Uchino et al [11]. This „downtime‟ highlights the difficulties of achieving truecontinuous RRT. Accordingly, physicians should be aware of the consequences of„downtime‟ on the true renal dose delivered when prescribing RRT on the ICU.Theideal prescribed dose for CRRT is not universally agreed upon, however, 35 ml/kg/hrof filtrate production is recommended to achieve a delivered dose of 20-25ml/kg/hrfor CvvH (post-filter dilution) and CvvHDF [12]. Even though the ATN and RENALtrials showed no mortality benefit to high intensity renal dosing in the general ICUpopulation, physicians should not assume there is not a role for individualisedprescribing in RRT. Given the variety of pathologies and patients encountered on thegeneral ICU, it is imperative to try and optimise individuals RRT.
    • Although mortality is an important outcome, it is vital to consider other incidentalbenefits of high intensity RRT, including the potential attenuation of SIRS/sepsisaccording to the humoral theory of sepsis. The RENAL trial did show a non-significant trend towards lower mortality in the septic patient subgroup(OR 0.84,95%CI 0.62-1.12), however, this was a post hoc analysis and the trial was not powered toirrefutably disprove this hypothesis [10]. The potential haemodynamic and organdysfunction benefits are well described in animal studies, but would need furtherhuman trials to delineate its role on the adult ICU [13].Learning points Early initiation of RRT in AKI should be considered when the underlying pathology is likely to persist. CRRT is better tolerated in the critically ill; however, there is no mortality benefit to any one particular RRT modality. There is no clear evidence for high intensity renal dosing in AKI for the general ICU population. High intensity renal dosing may have a role in inflammatory mediator clearance and adsorption in unresponsive septic shock.References 1. Rhodes A, Moreno RP, Metnitz B, et al. Epidemiology and outcome following postsurgical admission to critical care. Intensive Care Med 2011; 37:1466- 1472. 2. Basso F, Ricci Z, Cruz D, et al. International survey on the management of acute kidney injury in critically ill patients: year 2007. Blood Purif 2010;30:214- 220 3. Davenport A, Will EJ, Davidson AM, et al. Improved cardiovascular stability during continuous modes of renal replacement therapy in critically ill patients with acute hepatic and renal failure. Crit Care Med 1993; 21(3): 328-338. 4. Augustine JJ, Sandy D, Seifert TH, et al. Randomised controlled trial comparing intermittent with continuous dialysis in patients with ARF. Am J Kidney Dis 2004; 44(6): 1000-1007. 5. Honore PM, Jamez J, Wauthier M, et al. Prospective evaluation of short-term , high volume isovolemic hemofiltration on the hemodynamic course and outcome in patients with intractable circulatory failure resulting from septic shock.Crit Care Med 2000. Vol 28(11) 3581-3586. 6. Vinsonneau C, Camus C, Combes A, et al. Continuous venovenoushaemodiafiltration versus intermittent haemodialysis for acute
    • renal failure in patients with multiple-organ dysfunction syndrome: a multicentre randomised trial. Lancet 2006; 368:379-3857. VA/NIH Acute Renal Failure Trial Network. Intensity of renal support in critically ill patients with acute kidney injury. N Engl J Med 2008; 359:7-20.8. Ricci Z, Salvatori G, Bonello M, et al. In vivo validation of the adequacy calculator for continuous renal replacement therapies.Crit Care 2005;9:R266- R273.9. Ronco C, Bellomo R, Homel P, et al. Effects of different doses in continuous veno-venous haemofiltration on outcomes of acute renal failure: a prospective randomised trial. Lancet 2000; 356:26-30.10. RENAL Replacement Therapy Study Investigators. Intensity of continuous renal-replacement therapy in critically ill patients. N Engl J Med 2009;361:1627-1638.11. Uchino S, Fealy N, Baldwin I, et al. Continuous is not continuous: the incidence and impact of circuit "down-time" on uraemic control during continuous veno-venous haemofiltration. Intensive Care Med. 2003 Apr;29(4):575-8. Epub 2003 Feb 8.12. Standards and Recommendations for the provision of renal replacement therpy on intensive care units in the UK. Intensive Care Society standards and Safety. 01/2009.13. Bellomo R, Kellum JA, Gandhi CR, et al. The effect of intensive plasma water exchange by hemofiltration on hemodynamics and soluble mediators in canine endotoxemia. Am J RespirCrit Care Med 2000; 161:1429-1436
    • Case 7: Hyperbaric oxygen therapy in carbon monoxidepoisoningIntroductionAirway injuries as a result of house fires are thankfully not a common occurrence butcan have serious morbidity and mortality implications. Early priority should be givento securing the airway prior to airway obstruction following a direct airway burn. Oncethis is achieved, it is important to actively seek and manage the other respiratory andsystemic complications of smoke inhalation, carbon monoxide and cyanide poisoningfor example. Isolated bronchial or parenchymal injury due to soot related reactivepneumonitis requires meticulous ICU care and due to its relative frequencycompared to massive cutaneous thermal injuries, should fall within the remit of mostintensivists.Clinical problem and relevant managementA 59 year old gentleman with a background of hypertension was assessed in theEmergency Department (ED) resuscitation room with injuries sustained in a housefire. The local fire crew found the patient obtunded on the floor of his bedroom whichwasfilled with a significant amount of noxious smoke. When assessed on the sceneby paramedics he was noted to have a GCS of 5/15 with equal and reactive pupils.On assessment at the Emergency Department (ED), he had audible stertor andstridor, dysphonia, with evidence of soot in his nostrils and oropharynx. With pulseoximetry his saturations on 15L/min oxygen via a Hudson non-rebreath mask were98%, however the arterial blood gas revealed a PaO2 of 8.8kPa, PaC02 of 5.8kPa, acarboxyhaemoglobin level of 34%, a pH of 7.23, BE -7 and a lactate level of 1.9. Hewas haemodynamically stable and GCS had increased to 9/15. There were no burnor traumatic injuries.He was intubated in the ED without complication, however, soft tissue laryngealoedema was noted. Following a normal CT scan of his head he was subsequentlytransferred to the ICU.A bronchoscopy revealed significant carbonaceous materialthroughout the bronchial tree and an erythematous, friable mucosa with occasionalbleeding despite minimal point contact. Multiple therapeutic washouts wereundertaken and protective lung ventilation was instigated. Pressure controlventilation was utilised targeting a tidal volume of 6ml/kg of the ideal body weightand PEEP of 12cmH2O due to extensive basal atelectasis. Additionallythe local„inhalation protocol‟was started with regular chest physiotherapy. Part of the„inhalational protocol‟ was a triple nebulised therapy includingsalbutamol,unfractionated heparin and acetylcysteine. Oxygenation and lungcompliance improved dramatically within 72 hours and he was extubatedsuccessfully, neurologically intact.Given the lack of significant thermal injuries, the high admissioncarboxyhaemoglobin level and the low GCS at the scene, a debate occurred on
    • admission as to whether this gentleman would be appropriate for hyperbaric oxygentherapy. Due to the initial instability and equipoise regarding the clinical benefit, adecision was taken not to transport despite local bed availability.DiscussionCarbon monoxide (CO) is a colourless, odourless, non-irritating gas which is formedby incomplete hydrocarbon combustion. It can therefore be formed and inhaled inaccidental fires, and can also be produced by defective gas fires and heatingsystems. Rarely, methylene chloride, an industrial solvent can be ingested andmetabolised to CO by the liver.Physiologically, the affinity between haemoglobin and CO is approximately 230 timesstronger than that with oxygen, so haemoglobin preferentially binds to carbonmonoxideand consequently impairs oxygen transport causing hypoxaemia.CO exposure and poisoning often initially goes unnoticed due to the nature of thegas, and patients may be rendered unconscious before noticing exposure. Patientsmay complain of headache, nausea, dizziness and general malaise, althoughsymptoms of poisoning are highly variable. In severe cases, seizures, syncope,coma may occur, as well as cardiorespiratory and metabolic manifestations, such ascardiac arrhythmias, myocardial ischaemia, pulmonary oedema and lactic acidosis.Cardiac enzymes may be elevated and LVEF may be reduced, although mostmyocardial dysfunction resolves after treatment [1]. Delayed neurological sequelae,such as cognitive deficit, movement disorder and focal neurology can present up to240 days after exposure to CO [2].Diagnosis is largely based on history, examination and carboxyhaemoglobinpercentage.Pa02 can occasionally reflect p02 levels dissolved in plasma andtherefore may not be reduced. True co-oximetryhaemoglobin oxygen saturations areusually a more sensitive indicator of oxygen carriage. The severity of CO poisoningmaybe graded and deemed a mild (<20%), moderate (20-40%),severe (>40%) orfatal toxicity (>60%) according to the carboxyhaemoglobin percentage.COcauses endothelial cell release of nitric oxide, and the formation of oxygen freeradicals including peroxynitrite.These oxygen free radicals result in mitochondrialdysfunction, capillary leakage and leukocyte sequestration [3].The final commonpathway and mechanism for neurological injury is thought to be degradation ofunsaturated fatty acids and brain lipid peroxidation,which causes delayeddemyelinisation of white matter, oedema and cellular apoptosis [3].Clinical suspicion of cyanide poisoning, evidenced by an acidosis and highlyelevated lactate level, should be high in this clinical scenario, although this patienthad a normal lactate, mild metabolic acidosis and normal ScvO2, leaving theprobability of cyanide poisoning and histotoxic hypoxia unlikely [4].Standard management of CO toxicity in the acute setting involves high flow oxygentherapy to competitively bind with haemoglobin displacing the carbon monoxide. The
    • half-life of carboxyhaemoglobin decreases from 300 minutes to 90 minutes with highflow oxygen therapy.In recent years, the use of hyperbaric oxygen therapy (HBOT) as a treatment foracute CO toxicity has gained much interest in clinical practice due to the potential formitigating neurological sequelae. In theory, a higher pressure of oxygen allows amore rapid dissociation of CO from haemoglobin, but more importantly has apotential impact on cytochrome oxidase function and brain lipid peroxidation.There have been a multitude of conflicting results from various randomised controltrials looking at the use of HBOT in CO poisoning [5-9].Two out of the five RCTssuggested a potential benefit to HBOT, two were equivalent and one suggested anegative impact on morbidity [5]. Weaver et al in 2002 showed benefit following threehyperbaric oxygen treatments within 24 hours of presentation, with a reduced risk ofcognitive sequelae at 6 and 12 weeks post-acute toxicity [6]. This double-blindedtrial randomised patients into two groups of 76 patients: one group received onetreatment of normobaric oxygen followed by two treatments of normobaric air withinthe chamber in a 24 hour period, and the other group received three sessions ofhyperbaric oxygen treatments in the chamber over the same time frame. There wasa statistically significant reduction in neurological sequelae in the patients receivingthree hyperbaric oxygen treatments. A subsequent Cochrane review in 2005suggested that the two groups in this trial did not have appropriately matchedbaseline variables, and concluded that there is no evidence to promote the use ofhyperbaric oxygen in the prevention of neurological sequelae [10].Thus the evidence for the use of HBOT to prevent ongoing neurological sequelae,which themselves may have a delayed presentation after acute toxicity, is currentlylimited. A well-designed multicentre randomised controlled trial would be needed toconclusively delineate any benefit of HBOT in CO poisoning.Preliminary evidence supporting the use of C02 supplementation to allownormocarbic hyperventilation and increase CO displacement is promising, but as yetno randomised trial exists [11].Learning Points There is limited evidence for the use of hyperbaric oxygen therapy in the treatment of acute CO toxicity, and further trials are needed to elucidate the efficacy of its use. Other methods to increase minute volume may prove useful in the future.References 1. Kalay N, Ozdogru I, Cetinkaya Y, et al. Cardiovascular effects of carbon monoxide poisoning.Am J Cardiol. 2007 Feb 1;99(3):322-4. Epub 2006 29. 2. Kwon OY,Chung SP, Ha YR, et al; Delayed postanoxic encephalopathy after carbon monoxide poisoning.Emerg Med J 2004 Mar;21(2):250-1
    • 3. Hardy KR, Thom SR. Pathophysiology and treatment of carbon monoxide poisoning. Journal of Toxicology. Clinical Toxicology 1994;32 (6): 613–629.4. Baud FJ, Borron SW, Mégarbane B, et al. Value of lactic acidosis in the assessment of the severity of acute cyanide poisoning. Crit Care Med. 2002 Sep;30(9):2044-50.5. Scheinkestel CD, Bailey M, Myles PS, et al. Hyperbaric or normobaric oxygen for acute carbon monoxide poisoning: a randomized controlled clinical trial. MJAMarch 1999;170 (5): 203–210.6. Thom SR, Taber RL, Mendiguren II, et al.Delayed neuropsychologicsequelae after carbon monoxide poisoning: prevention by treatment with hyperbaric oxygen. Annals of Emergency Medicine. 1995;25 (4): 474–480.7. Raphael JC, Elkharrat D, Jars-Guincestre MC, et al.Trial of normobaric and hyperbaric oxygen for acute carbon monoxide intoxication. Lancet. August 1989; 8660: 414–419.8. Ducasse JL, Celsis P, Marc-Vergnes JP, et al. Non-comatose patients with acute carbon monoxide poisoning: hyperbaric or normobaric oxygenation?Undersea & Hyperbaric Medicine. March 1995; 22(1):9–15.9. Weaver LK, Hopkins RO, Chan KJ, et al.Hyperbaric oxygen for acute carbon monoxide poisoning.N Engl J Med. 2002 Oct 3;347(14):1057-6710. Juurlink D. Hyperbaric oxygen for carbon monoxide poisoning. Cochrane Database Syst Rev 2005;(1):CD00204111. Takeuchi A. A simple "new" method to accelerate clearance of carbon monoxide. Am J RespirCrit Care Med 2000 Jun;161(6):1816-9.
    • Case 8: Guillain Barré SyndromeIntroductionGuillain-Barré syndrome (GBS) is the most frequent cause of acute areflexicparalysis worldwide. The pathological process commonly involved is a multifocalinflammationof the spinal roots and peripheral nerves, especially theirmyelin sheathand rarely the axon themselves. Beyond supportive immediate care and meticulousrespiratory care, the precise role of plasmapheresis (PP) over intravenousimmunoglobulins(IVIG) remains contentious.Clinical problem and relevant managementA 68 year old gentleman was admitted with an unsteady gait and progressivesymmetrical weakness. On further questioning the patient had recovered from a fiveday upper respiratory tract infection a month previously. On examination there was a3/5 weakness below the elbow and knees with relative sparing of sensation. Therewas no cardiovascular abnormality and initial lung function tests were normal.Investigations of note included a lumbar puncture which showed an elevated proteinlevel, no white or red cells and a negative gram stain.A provisional diagnosis of GBSwas made and the patient was admitted to a medical ward where IVIG and seriallung function tests were undertaken.By day two of his admission his weakness had progressed and his lung function testhad deteriorated. Given a FVC of 1.4L, FEV1 of 0.9L and progressive type 2respiratory failure, the patient was intubated and ventilated. He completed a five daycourse of IVIG (2g/kg total) following which he had a percutaneous tracheostomy. Hemade a gradual neurological improvement over the following month despite a bout ofsepsis and moderate ARDS secondary to a ventilator associated pneumonia.However, between day 38 and 43 a worsening of his peripheral and respiratorymuscle weakness was noted. This was not felt to be in keeping with a critical illnessneuro-myopathy and more likely reflected a deterioration in his GBS. Followingdiscussion with various neurologists at a tertiary referral centre the decision wastaken to complete a second course of IVIG over a course of PP.Following a prolonged respiratory wean the patient was transferred to a long termweaning unit where he was eventually decannulated after 8 months. He wasdischarged home but required significant assistance from a zimmer frame tomobilise.DiscussionGBS is an acute ascending polyneuropathywhich can result in a progressive motordeficit, parasthesia and dysthesia. The muscle weakness tends to progress from thelimbs centrally to the trunk over a period of 12 hours to 28 days, resulting in asymmetrical paralysis, respiratory muscles weakness and potentially a significantautonomic dysreflexia. Two thirds of cases with this demyelinating condition arethought to have had exposure to a viral antigen, with upper respiratory tract
    • infections or diarrhea being common prodromal complaints. A number of viruseshave been implicated and include Campylobacter jejuni (30%), cytomegalovirus(10%), Epstein Barr virus, Varicella zoster virus, Haemophilusinfluenzae andMycoplasma pneumonia [2]. GBS covers a whole spectrum of subtypes that include: Acute inflammatory demyelinating polyneuropathy (AIDP) o Facial variant: Facial diplegia and paresthesia Acute motor axonal neuropathy (AMAN) o More and less extensive forms  Acute motor–sensory axonal neuropathy (AMSAN)  Acute motor-conduction-block neuropathy o Pharyngeal–cervical–brachial weakness Miller Fisher syndrome o Incomplete forms  Acute ophthalmoparesis (without ataxia)  Acute ataxic neuropathy (without ophthalmoplegia) o Central nervous system variant - Bickerstaff‟s brain-stem encephalitisA thorough history and neurological assessment is vital to establishing a diagnosis.Additional investigations which may assist in the diagnosis include a lumbarpuncture, nerve conduction studies and antiganglioside antibody. Cerebrospinal fluidmay demonstrate an albuminocytologic dissociationin 50% of GBS during the firstweekof illness or pleocytosis [2].An absent H response, abnormal F wave andabnormal upper extremity sensory nerve action potentials (SNAP) combined with anormal sural SNAP are characteristic of early GBS [3].Despite increasing availability of immunomodulation therapies, GBS is stillassociated with a 5% mortality rate and 20% of patients will go on to have apermanent neurological disability [1]. In developed countries with early access toinvasive ventilation the majority of the deaths are as a result of a medicalcomplication such as superimposed sepsis, immobility related pulmonary emboli andautonomic dysfunction related sudden cardiac arrest.Intubation and ventilation should be considered in patients who fulfill one major ortwo minor criteria [4]:Major criteria Hypercarbia- PaCO2>6.4 kPa Hypoxaemia – PaO2 (on FiO2 of 0.21)<7.5 kPa Vital capacity < 15 ml/kg ideal body weightMinor criteria
    • Inefficient cough – No accepted quantitative definition. Peak expiratory cough flow (PECF) <250L/min = Ineffective cough <160L/min = risk of repeated infections. Forced expiratory volume in one minute FEV1 <1L/min [5] Impaired or unsafe swallow – early assessment is essential and nasogastric tube insertion should be considered. Clinical or radiographic signs of atelectasisTwo recent Cochrane reviews have shown that PP orIVIG are effective in hasteningGBS recovery if administered within two weeks of symptom onset [6,7].Theindication for initiation of immunomodulation therapy is the inability to walkindependently [2]. Corticosteroids,interferon β-1a, brain-derived neurotrophicfactorand cerebrospinal fluid filtration have shown to be of no significant benefit in GBS [6].In PP, similar equipment tohaemofiltration is utilised but with a more porous filterdesigned to remove the plasma and high molecular weight pathogenic material(IgG/M, paraproteinsetc). Once the pathogenic material is removed, an equal volumeof substitute fluid (human albumin solution or fresh frozen plasma) is added to theblood cells and returned to the patient. A typical regime would include fiveexchanges involving the replacement of five plasma volumes [2]. A cochrane reviewhas shown that PP is more effective than supportive care alone in GBS [6].IVIG is thought to exert its effect by neutralising pathogenic antibodies andinhibitingautoantibody-mediated complement activation which results in reducedmyelin injury [2]. A typical course of IVIG in GBS would involve 0.4g/kg/day for fivedays [2].Treatment with IVIG is as effective as PP and is probably the treatment ofchoice given its greater safety, convenience and availability [2].The combination ofIVIG and PP has not been shown to be significantly more effective than either alone[7]. Limited evidence exists for a second course of IVIG in GBS patients that showno initial response or who deteriorate following a successful treatment [8].The cornerstone to GBS management is thorough respiratory care,immunomodulation therapy and rehabilitation, however, the intensivist must alsoensurethat thromboembolic prophylaxis, early enteral nutrition, good bowelmanagement and chronic pain issues are all addressed.Learning points Given the protracted timeline of the disease these patients require holistic multidisciplinary care that extends well beyond their acute care received on the intensive care. Early use of PP or IVIG have been shown to be equally efficacious in reducing the recovery from GBS. IVIG is probably the treatment of choice given its greater safety profile, convenience and availability.References
    • 1. Hughes RAC, Swan AV, Raphaël JC, et al. Immunotherapy for Guillain-Barré syndrome: a systematic review. Brain 2007;130:2245-57.2. Yuki N, Hartung HP. Guillain-Barré syndrome. N Engl J Med. 2012 Jun 14;366(24):2294-304.3. Gordon PH, Wilbourn AJ. Early Electrodiagnostic Findings in Guillain-Barré Syndrome. Arch Neurol. 2001;58(6):913-917.4. Burakgazi AZ, Höke A. Respiratory muscle weakness in peripheral neuropathies. J PeripherNervSyst2010;15:307-13.5. Howard RS, Davidson C. Long term ventilation in neurogenic respiratory failure.NeurolNeurosurg Psychiatry. 2003 Sep;74Suppl 3:iii24-30.6. Hughes RA, Pritchard J, Hadden RD.Pharmacological treatment other than corticosteroids, intravenous immunoglobulin and plasma exchange for GuillainBarré syndrome.Cochrane Database Syst Rev. 2011 Mar 16;(3):CD008630.7. Hughes RA, Swan AV, van Doorn PA.Intravenous immunoglobulin for Guillain-Barré syndrome.Cochrane Database Syst Rev. 2012 Jul 11;7:CD002063.8. Farcas P, Avnun L, Frisher S, et al. Efficacy of repeated intravenous immunoglobulin in severe unresponsive Guillain-Barré syndrome. Lancet 1997;350:1747.
    • Case 9: Extra Corporeal Membrane Oxygenation inRespiratory FailureIntroductionExtra Corporeal Membrane Oxygenation(ECMO) in is emerging as a usefulcomponent of an intensivist‟s armamentarium when caring for patients withsignificant respiratory and cardiovascular insults. In patients where conventionalventilation and adjuncts have failed, ECMO is the next logical consideration.However, benefits may also extend to limiting overdistension ofthe heterogeneouslyinjuredlungs and hopefully mitigate the effects of ventilator associated lung injury(VALI).Clinical problem and relevant managementParamedics were asked to attend a ten year old suffering from an asthmaexacerbation. The boy was a known brittle asthmatic with one previous PICUadmission, regular inhaled steroids and leukotriene antagonist orally. On arrival theboy was tachypnoeic with a silent chest, hypoxic on room air and was somnolent. Hewas given high flow oxygen, 0.25mcg IM epinephrine, nebulised salbutamol andipratropium bromide. Despite these measures the patient became apnoeic intransport necessitating bag valve mask ventilation and bilateral needlethoracocentesis without obvious release of a tension pneumothorax. Within a fewminutes bradycardia progressed to a full cardiorespiratory PEA arrest and wasmanaged using standard advanced life support algorithms. The patient arrived in theED nine minutes later. Intubation, bilateral open thoracostomies and a further 15minutes of CPRwere requiredprior to return of spontaneous circulation (ROSC).Following ROSC the main problem encountered was hypoxia and persistent severebronchospasm with respiratory acidaemia (pH 6.67). To address the bronchospasma myriad of therapies were trialled and failed, including nebulisers,epinephrine/ketamine infusions, magnesium sulphate, hydrocortisone and inhaledvolatile anaesthetics. Given the failure of all bronchodilator therapies and the needfor neuroprotection following the cerebral insult sustained during the cardiac arrest, adecision was taken to place the child on venovenous ECMO.21F right femoral vein (drainage line) and 19F right internal jugular vein (return line)cannulas were sited and systemic anticoagulation was achieved with unfractionatedheparin. Attempts to achieve adequate flow was hampered by persistent sucking onthe drainage cannula and further fluid resuscitation was required.Once adequateblood flow was achieved there was a rapid improvement in oxygenation and gasexchange, with a pH greater than 7.25within 30 minutes of initiation.As partof a specialist retrieval service (doctor, paramedic and perfusionist),I wastasked with managing the transfer of this patient to a paediatric ECMO centre.Greater Sydney area HEMS are the designated service for transfer of any patientsrequiring intra-aortic balloon pump or ECMO support. The patient was optimised pre-
    • transfer by increasing the blood flow to 2.3 L/min and sweep gas to 5L/min to ensureadequate oxygenation, normocarbia and neuroprotection. Ketamine, midazolam,fentanyl, heparin and epinephrine infusion were adjusted and volatile anaestheticswere weaned. Ultra-protective lung ventilation with a TV of 3ml/kg, PEEP of 10cmH2O, RR 6 and a FiO2 of 0.4 was employed. Targeted temperature managementwas started and a temperature of 34°C was attained within two hours of the arrest.The patient was transferred in a specialist retrieval road ambulance uneventfully.Subsequent rapid improvement in the patient‟s bronchial smooth muscle tone andlung compliance, allowed the ECMO to be weaned off in 48 hours. Followingdiscontinuation of sedation, the patient remained in a minimal conscious state withan MRI consistent with significant anoxic brain injury. The patient was still aninpatient at the time of completing this case summary.Figure 1. ECMO retrieval stretcher with bridge that holds the maquet ECMO pump,circuit, hand crank, Lifepak 15 monitor and oxylog 3000+ ventilator
    • Figure 2. View of stretcher and bridge in the ambulanceDiscussionECMO is a form of extracorporeal life support where an outside artificial circulationconveys venous blood from the patient to a gas exchange device(oxygenator) whereblood becomes enriched with oxygen and carbon dioxide is removed. The use ofECMO in patients where adequate oxygenation and gas exchange cannot bemaintained despite optimal conventional respiratory care would seem intuitive, but itmay also allow ultra-protective lung ventilation to limit shearing forces and furtherVALI. While the following discussion will concentrate on peripheral ECMO, inpractice the clinician may come across centralECMO (Figure 3) and AVextracorporeal CO2 removal (interventional lung assist, Novalung) depending on theclinical situation and local preferences.
    • Figure 3. Central VA ECMOThe modality of peripheralECMO utilised will depend performed will depend on thepatient‟s underlying cardiac function. Venovenous (VV) ECMO is usually undertakenfor isolated respiratory failure, while venoarterial (VA) ECMO is instigated forcombined cardiac and respiratory failure.VV ECMOinvolves removal of venous blood from the patient‟s central veins via awire reinforced access/drainage cannula. The blood then passes through a pump,typicallya centrifugal rather than a roller pump to limit haemolysis [1]. After the pumpthe blood flows through the oxygenator and returned to the venous systemvia areturn linenear the right atrium. Oxygenation and carbon dioxide excretion can beoptimised by altering the blood flow and oxygen sweep gas respectively. Therequired blood flow in VV ECMO is classically 2/3 of the patient‟s cardiac output (60-70ml/kg/min) while the sweep gas flow rate will usually be double that of the bloodflow rate. If attempts to improve oxygenation by increasing blood flow fail, thepossibility of recirculation between the drainage and return cannula should beconsidered.Other possible set ups seen in VV ECMO include a second venous drainage cannulain high flow VV ECMO or use of a single Avalon (dual lumen) cannula.
    • Figure 4. VV ECMO circuitVA ECMO involves venous blood from the patient being accessed from thelargecentral veins and returned to a major artery after it has passed through thepump and oxygenator. It providessupport for severe respiratory and cardiac failure.Low flow VA ECMO is a temporary form of ECMO support in which smallcannulaeare inserted percutaneously. This is often referred to asECMO-CPR (E-CPR) or Extracorporeal lifesupport (ECLS) and is merely a temporising circuit set upin the emergent situation.All forms of ECMO need anticoagulation to limit circuit thrombosis and complications.With newer heparin bonded lines the anticoagulation requirements are lower andtypically an ACT of 180-220 should be targeted.Figure 5. VA ECMO circuit
    • ECMO is indicated for potentially reversible, life-threatening forms of respiratory andcardiac failure, which has failed to respond to conventional therapy. Indicationsinclude: Pathology amenable to VV ECMO Common indications Severe pneumonia ARDS Acute lung (graft) failure following transplant Pulmonary contusion Common indications Alveolar proteinosis Smoke inhalation Status asthmaticus Airway obstruction Aspiration syndromes Pathology amenable to VA ECMO Common indications Cardiogenic shock, myocardial infarction and complications, refractory to conventional therapy including IABP Post cardiac surgery: unable to wean safely from cardiopulmonary bypass using conventional supports Drug overdose with profound cardiac depression Myocarditis Early graft failure: post heart / heart-lung transplant Septic cardiomyopathy Uncommon indications Pulmonary embolism Cardiac or major vessel trauma Massive haemoptysis / pulmonary haemorrhage Pulmonary trauma Acute anaphylaxis Peri-partum cardiomyopathy Bridge to transplantEarly RCTs were unable to demonstrate any survival benefit with ECMO [2,3]. Nosurvival benefit coupled with a worryingly high incidence of uncontrolled bleedingeventswhilst anticoagulated,limited the uptake of the technique [3]. However, overthe last decade there has been a growing body of evidences to suggest that ECMOmay be beneficial in well selected patient groups[4-8]. This survival benefit could be
    • explained by the greater application ofprotective lung ventilation strategies andadjuncts as well as the improved ECMO technology.The CESAR trial published in 2009,was a RCT thatshowed patients with severerespiratory failure (Murray score >3 and pH<7.2) that were managed in an ECMOcapable institution had a 16% absolute risk reduction of death or severe disability atsix months(RR=0.69, CI 0.05-0.97, p=0.03).This adequately powered studyrandomised 180 patients in a 1:1 ratio to either a control arm of local institutionmanagement or transfer to a specialist ECMO facility. Of the patients assigned totransfer to the specialist ECMO facility; 68 (75%) received ECMO, 17 hadconventional management, 3 died before transport and 2 died in transit.Encouragingly, this true intention to treat analysis, use of traditional roller pumps andhigh dose anticoagulation may have actually diluted the potential benefits of ECMO.A few potential concerns do exist with the trial. The major concern is that patients inthe control arm were managed across a number of centres with no specificmanagement protocol. The importance of protective ventilation strategies is wellknown [9], however, only 70% of patients in the control arm were ventilated inaccordance with this evidence [7]. This control arm were also not directly comparedto patients receiving ECMO, as only 75% of patients in the intervention groupreceived ECMO [7]. The intervention group were managed using a standardisedprotocol which utilised protective lung ventilation strategies and then potentiallyprone ventilation, HFOV, inhaled NO and ECMO [7]. So potentially some of theperceived benefit could be related to the standardised protocol treatment and notpurely ECMO.The novel influenza (H1N1) pandemic in 2009 highlighted the potential benefits ofECMO in severe viral respiratory failure [8,10]. The reported hospital mortality ratesof 21-27.5% are far lower than any previously published data [8,10]. From the 4400patients described in the extracorporeal life support registry report we know thesurvival rates from viral pneumonia are high comparatively to other ECMOindications [11]. This in combination with a young median age of 34.4 and low ratesof MODS would probably explain the high survival rates. However, this trial is one ofthe largest recent observational ECMO cohort and it may reflect also reflect animprovement in technology. The Greater Sydney HEMS were involved in the transferof 40 patients with novel influenza [12]. Following ECMO initiation in the referringinstitution, there were no deaths during transfer by our specialist retrieval service,compared to the two deaths in the CESAR trial [7,12].Emergent, low flow VA ECMO, often referred to as ECMO-CPR (E-CPR) orextracorporeal lifesupport (ECLS) is a potential new use for ECMO in refractorycardiac arrest. In a prospective, observational trial with propensity-score matchedgroups there was a significant improvement in one year survival (18.6% vs 9.7%,p=0.006) between E-CPR and conventional resuscitation [13]. Clearly careful patientselection is vital here to ensure desirable survival rates, while limiting poorneurological outcomes.
    • Learning points ECMO technology is continuously evolving and improving. There may be a survival benefit when ECMO is employed in a well selected subgroup of patients with severe respiratory and cardiac failure.References 1. Lawson DS, Ing R, Cheifetz IM et al. Hemolytic characteristics of threecommercially available centrifugal blood pumps. PediatrCrit Care Med2005;6:573-77. 2. Zapol WM, Snider MT, Hill JD et al. Extracorporeal membrane oxygenation in severe acute respiratory failure. A randomized prospectivestudy. JAMA 1979;242:2193-96. 3. Morris AH, Wallace CJ, Menlove RL et al. Randomized clinical trial ofpressure-controlled inverse ratio ventilation and extracorporeal CO2removal for adult respiratory distress syndrome. Am J RespirCrit Care Med1994;149:295-305. 4. Mols G, Loop T, Geiger K et al. Extracorporeal membrane oxygenation: aten- year experience. Am J Surg 2000;180:144-54. 5. Beiderlinden M, Eikermann M, Boes T et al. Treatment of severe acuterespiratory distress syndrome: role of extracorporeal gas exchange.Intensive Care Med 2006;32:1627-31. 6. Hemmila MR, Rowe SA, Boules TN et al. Extracorporeal life support forsevere acute respiratory distress syndrome in adults. Ann Surg 2004;240:595-607. 7. Peek GJ, Mugford M, Tiruvoipati R et al. Efficacy and economic assessment of conventional ventilator support versus extracorporealmembrane oxygenation for severe adult respiratory failure (CESAR): amulticentre randomized controlled trial. Lancet 2009;374:1351-63. 8. Noah M, Peek G, Finney S et al. Referral to an extracorporeal membraneoxygenation center and mortality among patients with severe 2009influenza A (H1N1).JAMA 2011;306:1659-68. 9. The Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000 May 4;342(18):1301-8. 10. Davies A, Jones D, Bailey M et al. Extracorporeal membrane oxygenation for 2009 influenza A (H1N1) acute respiratory distress syndrome. JAMA 2009;302:1888-95. 11. Extracorporeal Life Support Organization (ELSO). ECMO Registry Report of theELSO: International Summary. ELSO, Ann Arbor, Michigan; January 2011.
    • 12. Forrest P, Ratchford J, Burns B, et al.Retrieval of critically ill adults using extracorporeal membrane oxygenation: an Australian experience.Intensive Care Med. 2011 May;37(5):824-30. Epub 2011 Feb 26.13. Chen YS, Lin JW, Yu HY et al. Cardiopulmonary resuscitation withassisted extracorporeal life-support versus conventional cardiopulmonary resuscitation in adults with in-hospital cardiac arrest: an observational study and propensity analysis. Lancet 2008;16;372:554-61.
    • Case 10: New and novel strategies for managingpropranolol overdoseIntroductionBeta blockers (BB) have been a commonly prescribed cardiovascular medication forover 30 years. BB toxicity can have significant cardiovascular complications that maybe refractory to standard medications used for circulatory support. BBsare oftenoverrepresented when it comes to cardiovascular medication deaths.Clinical problem and relevant managementA 20-year old female presented to her local ED three hours post ingestion of 20 unitsof alcohol and approximately 1.6g of propanolol (40x tablets of 40mg). There was noverbalised suicidal ideation, suicide note, or previous suicide attempts.On initialassessment she had a heart rate of 46 bpm, BP 92/60, SpO2 99% on FiO2 0.6,respiratory rate of 22 and was drowsy with a GCS 11/15. Her ECG showed firstdegree heart block with a PR interval of 210ms, QRS duration 128ms, QTc interval420ms. The patient was intubated, received three 600mcg doses of atropine, 50mmol of sodium bicarbonate, titrated fluid resuscitation and 50g of activatedcharcoal. Despite these measures the patient remained hypotensive andbradycardic. An epinephrine infusion was started to maintain mean arterial pressureof 65mmHg and further 50mmol of Sodium bicarbonate. Due to the extreme doses ofepinephrine (approaching 0.4mcg/kg/min) and the ECG abnormalities, the patientwas discussed with the regional poisons unit which advised further plasmaalkalinisation and high dose insulin therapy. Epinephrine requirements quicklyreduced once the pH reached 7.4 and an insulin infusion was established at a steadyrate of 20u/hr.The patient wasextubated on day three of her ICU admission following anappropriate neurological wake up and was discharged from hospital on day five withappropriate psychiatric follow up.DiscussionPropranolol is a non-cardioselective beta blocker with sodium-channel blockingeffects. Its pertinent pharmacodynamics and pharmacokinetics are: Absorption: Rapidly absorbed orally. Peak blood levels occur at 1-3 hours following oral administration. Mechanism of action - Competitive antagonism of beta receptors leads to decreased intracellular cAMPmediated by G-protein transmembrane receptors. This ultimately results in blunting of the chronotropic, inotropic and metabolic effects of catecholamines. Unlike other beta blockers, propanolol and sotalol also block sodium-channels in the myocardium resulting in prolongation of the cardiac action potential with widening of the QRS complex
    • and potentially ventricular arrhythmias. Blockade of sodium channels in the CNS produces neurotoxic effects. Distribution: Highly lipophilic agent (93% protein bound) with a high volume of distribution. Rapidly distributed to all tissues. Metabolism: Undergoes extensive hepatic metabolism, with hydroxylation of the aromatic nucleus and degradation of the isoprenaline side-chain. Over 20 metabolites identified. The 4-hydroxy metabolite has active beta-blocking properties. Elimination: 95-100% of an ingested dose is excreted in the urine as metabolites and their conjugates. Half-life: Plasma half-life is around 3-6 hours. The pharmacological effects last much longer than this. Elimination half-life is 12 hours and may be prolonged following overdoseFigure 1. PropanololFigure 2. Effect of Na channel blockers on cardiac action potentialTypical features of BB toxicity include: Hypotension, bradycardiaand progressive cardiogenic shock.
    • Bradyarrhythmias – Sinus bradycardia, junctional or ventricular bradycardia, prolonged PR interval, atrioventricular block (1st-3rd degree). Bronchospasm Hyperkalaemia Hypo/hyperglycaemiaIn addition to other BBs, propanololwith its sodium channel blockade can cause: Cardiotoxicity – broad QRS (> 100 ms in lead II), right axis deviation of the terminal QRS, ventricular arrhythmias and cardic arrest in high doses. QRS > 160 ms is predictive of ventricular arrhythmias. Neurotoxicity – coma, seizures and delirium. QRS > 100ms predictive of seizures.ManagementAdult patients that have ingested greater than 1g of propanolol are at significant riskof sudden cardiac dysrhythmias and death, and should be managed in a critical carearea. The initial approach for evaluating the critically poisoned patient focuses onthorough assessment, appropriate stabilisation and supportive care.Such individualsshould be managed utilising the standard ABCDE approach. Consideration shouldbe given to early intubation and ventilation in patients with neurotoxicity, as this willallow acid-base balance optimisation and airway protection if activated charcoal(1g/kg) gut decontamination is considered. Serial 12-lead ECGs should beperformed to assess for beta and sodium-channel blockade. Seizures should bepromptly treated with intravenous benzodiazepines with the addition of sodiumbicarbonate if QRS > 100ms. Followingthe initial standardised approach to thepoisoned patient, it is vital to addressany signs β-adrenergicreceptor and sodiumchannel toxicity.Propranolol has profound effects on cardiac performance and can result in increasedLVEDP, left ventricular dP/dt max, stroke volume and cardiac output [1-3]. First linemanagement of hypotension is titrated crystalloid resuscitation. If this does notachieve an adequate cardiac output, blood pressure and end organ perfusion, thereshould be a low threshold for the use of inotropes and chronotropes. Repeateddoses of atropine (20 mcg/kg) can be used as a temporising measure for abradycardia related low cardiac output state. Persistent bradycardiadespite atropineassociated with hypotension is better treated with a titrated infusion of epinephrine,norepinephrine or isoprenaline.Glucagon was traditionally thought to be an “antidote”to BB toxicity as it directly stimulated adenylylcyclase resulting in increasedintracellular cAMP[4,5].Its clinical application is limited by the prohibitively high dosesrequired and the possible toxicity of the solvent phenol that is utilised in glucagonproduction [4].If any kind vasoactive infusion is required consideration should be given to earlyinitiation of high-dose insulin euglycaemic therapy (HIET).HIET should be cautiouslyinitiated and monitored intensively with an preliminarydose of 0.5 U/kg over 30
    • minutes, followed by a 0.5–1 U/kg/Hr continuous infusion [2,4,5]. To maintaineuglycaemia and normokalaemia, an infusion of between 15-30g/Hr of glucose andpotassium supplementation will be required [2].Insulin promotes glycogenesis andcellular glucose uptake, while inhibiting gluconeogenesis, β-oxidation and lipolysis[4]. Insulin also is known to exhibit inotropic effects in myocardium that has beendepressed by various insults [6]. Reikeras et al has extensively studied thehaemodynamic and metabolic effects of insulin therapy in BB overdose [1,5]. Theseanimal models demonstrated that HIET improves cardiac function with an improvedstroke volume and cardiac output [1,2,5].The inotropic effects of insulin seem to be dose dependent and unrelated toadrenergic mechanisms [2].Improvement of cardiac function in HIET is notassociated with an increase in myocardial oxygen consumption [1,4]. Reikeras et aldemonstrated that HIET did not alter myocardial bloodflow and oxygen consumptiondespite the significantimprovement in cardiac contractility [1]. While more clinicaltrials are needed, animal studies and human case reports have shown that in BBtoxicity HIET is associated with improved mortality, and maybe superior to glucagonor epinephrine infusions alone [7].It is hypothesised that intravenous lipid emulsion therapy exerts its beneficial effectsby expanding the plasma lipid sink, with consequentreduction in free drug level [8].Propanolol is a highly lipophilic and protein bound drug that in overdose may beamenable to lipid emulsion therapy. Currently there is only a limited evidence base tosuggest that intravenous lipidemulsion may be helpful in potentially lethal propranololoverdoses [9-11]. Lipid emulsion therapy should probably only be considered whenthere is extreme haemodynamic instability or cardiac arrest refractory to othermeasures[8].Figure 3. Suggested dosing for Lipid emulsion therapy [8].
    • Sodium channel blockade management is vital to a successful outcome inpropanolol toxicity and involves: Sodium bicarbonate is used to treat acidaemia, while improving the prolonged cardiac action potential and QRS prolongation [4]. If QRS>100ms, haemodynamically unstable or in cardiac arrest. o Sodium bicarbonate 1-2 mmol/kg) bolus every few minutes while monitoring the effect on ECG and haemodynamic response. o Consider further sodium bicarbonate bolus or infusion once stable to maintain pH 7.5- 7.55 based on hourly blood gas and QRS <100ms. o Boluses of sodium bicarbonate are likely to be more effective than infusions because they will lead to rapid shifts in the concentration of free drug. Intubate as soon as possible and hyperventilate to maintain a pH of 7.50 – 7.55 in combination with sodium bicarbonate. This helps to minimise pH related cardiotoxicity. Lignocaine (1.5mg/kg) IV can be utilised if ventricular arrhythmias persist following sodium bicarbonate and hyperventilation have achieved a pH > 7.5. In established cardiotoxicity, the dose of sodium bicarbonate can be repeated every few minutes until the BP improves and QRS complexes begin to narrow. Avoid Vaughan William classification drugs from classes Ia (procainamide), Ic (flecainide) and III (amiodarone) as they could worsen conduction defects and cardiovascular instability [4].In addition to the above measures haemoperfusion and VA ECMO have also beendescribed, but there are currently only a few specialist centres with limitedexperience [4].Learning points The care of a critically ill poisoned patient should involve appropriate investigation, monitoring and initial resuscitation, accompanied by optimisation of absorption, decontamination, elimination and potential use of antidotes. In patients who remainhaemodynamically unstable despite vasoactive infusions, consideration should be given to early initiation of HIET. Propanolol and sotalol have significant sodium channel blocking effects which need meticulous acid-base balance management in overdose.
    • References 1. Reikeras O, Gunnes P, Sorlie D, et al. Haemodynamic effects of low and high doses of insulin during beta-receptor blockade in dogs. ClinPhysiol 1985, 5:455-467. 2. Lheureux PER, Zahir S, Gris M, et al. Bench-to-bedside review: Hyperinsulinaemia/euglycaemiatherapy in the management of overdose of calcium-channel blockers. Crit Care. 2006;10(3):212. Epub 2006 May 22 3. Kerns W 2nd, Schroeder D, Williams C, et al. Insulin improves survival in a canine model ofacute beta-blocker toxicity. Ann Emerg Med 1997, 29:748- 757. 4. Kerns W. Management of b-Adrenergic Blocker and Calcium ChannelAntagonist Toxicity.Emerg Med Clin N Am 2007: 25:309–331. 5. Reikeras O, Gunnes P, Sorlie D, et al. Metabolic effects of low and high doses insulin during beta-receptorblockade in dogs. ClinPhysiol 1985, 5:469-478. 6. Krukenkamp I, Sorlie D, Silverman N, et al. Direct effect of high-dose insulin on the depressed heart after betablockade or ischemia. ThoracCardiovascSurg 1986, 34:305-309. 7. Kerns W 2nd, Schroeder D, Williams C, et al. Insulin improves survival in a canine model ofacute beta-blocker toxicity. Ann Emerg Med 1997, 29:748- 757. 8. Cave G, Harvey M. Intravenous Lipid Emulsion as AntidoteBeyond Local Anesthetic Toxicity: A Systematic Review. AcadEmerg Med. 2009 Sep;16(9):815-24. 9. Bania T, Chu J, Wesolowski M. The hemodynamic effect of Intralipid on propranolol toxicity. AcadEmerg Med. 2006; 13 S1):109. 10. Harvey M, Cave G. Intralipid infusion ameliorates propranolol induced hypotension in rabbits. J Med Toxicol. 2008; 4:71–6. 11. Harvey M, Cave G. Lipid emulsion may augment early blood pressure recovery in a rabbit model of atenolol toxicity. J Med Toxicol. 2009; 5:50–1.