This patient is a 25 year old female admitted to the ICU for respiratory failure and hypotension following a 6 day prodromal illness. She is intubated and receiving vasopressors. The differential diagnosis includes sepsis, severe sepsis, or septic shock from an unknown source. Principles of management include identifying the source, administering appropriate antibiotics, optimizing hemodynamics and organ function, and providing lung protective ventilation for her acute respiratory distress syndrome. Early enteral nutrition is important to support her systemic immune response and prevent further organ dysfunction from a cumulative energy deficit.

1. Intensive Care MedicineTopics for the Final FRCADr. Andrew Ferguson

2. Why ICU matters for the FRCA…20 specific questions in MCQHelps with medicine/surgery MCQsSAQs - 1 or 2 questions for sure…maybe moreSOE 1 - potential topic/part of topicSOE 2 - 10 minutes of pure fun!

3. Be calm…The examiners are human (honestly!!!)The questions are (mostly) mainstreamYou will have seen many of the casesGuillain-Barre / Myasthenic crisis / weaknessBrainstem death Status epilepticus and asthmaticusTraumaSeptic shockARDSAcute pancreatitisBurnsSome questions just won’t lie down and die e.g. PAC

4. But don’t be complacent…People still fail the exam! 10/17 passed in 2008Don’t assume you know enough…make sure you doStructure…structure…structure!Don’t waffle - answer the actual question, not the one you wanted to be asked!!

5. Other potentials…Acute hepatic failure

6. Sedation

7. Fluid balance and outcome

8. Nutritional therapy

9. Tissue oxygenation and oxygen delivery

10. Abdominal compartment syndrome

11. Cardiogenic shock

12. Clostridium difficile

13. Scoring systemsExamples…In the question on the brain-stem dead patient, too many candidates included detail of brain stem testing in their answers, which was not required. Candidates are reminded to answer the question as written; no credit will be given for irrelevant informationIt cannot be emphasised enough that the answer provided to the examiners is less than a page and is focused completely to the question.

16. Case scenario 149 year old female, history of depression & anxiety found unconscious in apartment having failed to turn up for workOn arrival A&E GCS 5-6, BM = 0.4After 50ml 50% glucose BM = 14.5 and GCS 12-14Bruising left buttock and thighTender abdomen, jaundiced, BP 75/45, HR 104, Temp 34.1CT brain NAD, CT abdo - mild hepatomegaly, ? fattyLabs: Lactate 10.2, Bili 27, AST 4465, ALT 1945, INR 4, Paracetamol 25, tox negative, K 1.9, Ca 0.8, PO40.4, Hb 10.4, WBC 15.9, Plts 102, CK 595

17. Questions for discussionWhat are the main differential diagnoses?What other information/tests would you like?Why is the GCS abnormal?How do you assess fluid status and responsiveness?What does the lactate level tell you?Why is the B low and how will you tackle it?How do you assess the adequacy of oxygen delivery?Does this patient need antibiotics?What problems are likely in the next 24-48 hours?

18. INFOAcute hepatic failure“Life-threatening multi-system illness resulting from massive liver injury. The defining clinical symptoms are coagulopathy and encephalopathy occurring within days or weeks of the primary insult in patients without pre-existing liver injury”Auzinger G, Wendon J. Curr Opin Crit Care 2008; 14: 179-188Early death despite supportSurvival with supportive therapy (liver regeneration)Unlikely to survive with supportive therapy alonecandidate for emergency transplantNOT candidate for emergency transplant

19. INFOAetiology based therapy

20. INFOParacetamol toxicityMajor pathsEnhanced riskExcessalcoholEnzyme-inducing drugscarbamazepine phenytoin, phenobarbitone St John's Wort rifampicin3. Glutathione depletion malnutrition eating disorders malabsorption HIVMinor pathNAPQI

21. N-acetylcysteineINFO(1) Initially 150mg/kg in 200mL glucose 5% given over 15 minutes, then(2) 50mg/kg in 500mL glucose 5% given over 4 hours, then(3) 100mg/kg in 1000mL glucose 5% given over 16 hours

22. INFOParacetamolReferral criteriaNon-paracetamol

23. INFONon-paracetamolParacetamolReferral criteria - Kings College Hospital

24. Clinical Issues in ALFINFOCNSEncephalopathy - ammonia => glutamateIntracranial hypertension - oedemaCardiovascularIntravascular volume depletionVasodilatationSubclinical myocardial damage (Tn > 0.1 in 66%)RespiratoryHypoxia - effusions, atelectasis, shunting, splinting, ALI

25. Clinical Issues in ALFINFORenalOliguriaAcute renal impairment - drugs, hepatorenal, pre-renal, ATN, intra-abdominal hypertensionHaematologicalThrombocytopaenia and coagulopathy Procedural bleeding possibleSpontaneous bleeding rareInfection Monocyte (HLA-DR), complement, Kupffer cell failureResponsible for most deaths!

26. INFOUseful references Kramer DJ, Canabal JM, Arasi LC. Application of Intensive Care Medicine Principles in the Management of the Acute Liver Failure Patient. Liver Transplantation 2008; 14: S85-89. Auzinger G, Wendon J. Intensive Care Management of Acute Liver Failure. Current Opinion in Critical Care 2008; 14: 179-188. Stravitz T. Critical Management Decisions in Patients with Acute Liver Failure. Chest 2008; 134: 1092-1102.

27. Case scenario 256 year old male, history of IHD/PVD/smoker/MI/EF 35%Admitted to ICU following emergent leaking AAA repair…complicated by intraoperative ST depression and hypotensionOn arrival ICU BP = 90/45, HR 121 SR, NA @ 0.5 mg/kg/min, lactate 5CVP 14, pO2 11 on 70% O2with PEEP 5, creps bilaterallyECG: infero-lateral ST depressionIn theatre 4 L crystalloid, 2 L tetraspan, 6 packed cells, 2 FFPAbdomen distended and tense, skin clammyOver next 4 hours: NA increasing, lactate 8, U/O poorLabs: Hb 9.5, Plts 85, WBC 7.9, Na 141, K 5.3, U 10.5 Creat 168, APTT 47, PT 18, fibrinogen 0.95

28. Questions for discussionList the main clinical issues in this caseHow would you approach the respiratory failure?What factors contribute to the hypotension/malperfusion?What is your strategy to improve haemodynamics?What is your target for fluid balance in the next 24 hours?How does PPV assist the left ventricle?What other monitors/investigations might assist you?When would you involve the surgeons?

29. INFOCardiogenic ShockDefinition

30. Incidence

31. Aetiology

32. Pathophysiology

33. TherapyClinical: Hypotension i.e. SBP below 90 mmHg

34. Impaired tissue perfusion

35. After correction of non-cardiac factorsHaemodynamic:Cardiac index < 2.2 litres/min/m2

36. Systolic blood pressure < 90 mm Hg

37. LAP/RAP > 18 mm Hg or PCWP > 16

38. Urine output < 20 ml/hr

39. SVR > 2100 dynes-sec·cm–5INFOIncidence & Mortality[1] The CREATE-ECLA Trial Group. Effect of glucose-insulin-potassium infusion on mortality in patients with acute ST-segment elevation myocardial infarction: the CREATE-ECLA Randomized Controlled Trial. JAMA 2005; 293: 437–446.[2] Babaev A, Frederick PD, Pasta DJ, et al. Trends in management and outcomes of patients with acute myocardial infarction complicated by cardiogenic shock. JAMA 2005; 294:448–454.[3] Jeger RV, Harkness SM, Ramanathan K, et al. Emergency revascularization in patients with cardiogenic shock on admission: a report from the SHOCK trial and registry. Eur Heart J 2006; 27:664–670.[4] Chen ZM, Pan HC, Chen YP, et al. Early intravenous then oral metoprolol in 45,852 patients with acute myocardial infarction: randomized placebo controlled trial. Lancet 2005; 366:1622–1632.

40. INFOEcho indicators of mortality

41. INFOPathophysiology

42. INFOCardiogenic ShockDefinition

43. Incidence

44. Aetiology

45. Pathophysiology

46. TherapyINFOPathophysiologyTarget for therapy?At least 20% of CS patients have SIRS and low SVR

47. INFOTherapy- Reducing iNOSEffect of Tilarginine Acetate in Patients With Acute Myocardial Infarction and Cardiogenic Shock - The TRIUMPH Randomized Controlled Trial. JAMA 2007; 297: 1657-1666 “Excessive NOS results in high levels of nitric oxide that, in turn, lead to inappropriate systemic vasodilatation, progressive systemic and coronary hypoperfusion, and myocardial depression”

48. INFOCardiogenic Shock: TherapyOptimise volume / oxygenation / rhythm

49. Inotropic agents & vasopressors

50. b agonists

51. a agonists

52. PDE III inhibitors

53. LEVOSIMENDAN

54. sensitizes myocardial contractile proteins to calcium

55. independent of sympathetic NS and so NO increase in MVO2

56. Prolonged action beyond infusion duration

57. IABP

58. PCIINFOAbdominal compartment syndromeIncreasingly recognised problemLOOK for it! - don’t forget “medical” ICU patientsThinks about screening ifLarge volume resuscitation > 3.5 L in 24 hoursAbdominal Surgery/Primary Fascial ClosureCoagulopathy or polytransfusionPulmonary, renal or hepatic dysfunctionAcidosisHypothermiaIleusPhysical exam is NOT accurate

59. INFOIntra-abdominal pressureAbdominal perfusion pressure = MAP - IAP (aim > 60 mmHg)

60. INFOAbdominal CompartmentSyndromeACS = sustained IAP > 20 mmHg (with or without APP < 60 mmHg) that is associated with new organ dysfunction/failureWorld Society of the Abdominal Compartment Syndrome (www.wsacs.org)

61. INFO

62. INFO

63. Case scenario 325 year old female, “fit and well”Admitted to ICU after 6 day prodromal illness (fever, aches) followed by confusion, shortness of breath and now fluid-resistant hypotensionIntubated in A&E as hypoxic and combative, received 3 L salineOn arrival ICU BP = 75/40, HR 135 SR, NA @ 0.7 mg/kg/min, lactate 7, CVP 9, pO2 9 on 100% O2with PEEP 7, creps bilaterallyTemperature 39.7, flushedOver next 2 hours: NA increasing, lactate 9, U/O poorLabs: Hb 10.5, Plts 65, WBC 27.9, Na 137, K 3.3, U 12.5 Creat 138, APTT 47, PT 19, fibrinogen 1.0, CK 290

64. Q: Comments on Xray appearance?

65. Questions for discussionWhat is the differential diagnosis?What are the possible sources?What are the principles of management?Describe your haemodynamic targets and approachHow do you make the diagnosis of ARDS?What ventilator settings will you choose?What principles guide your ventilation strategy?What are your ventilator targets?

66. Sepsis: Know what you mean…INFOSIRS - 2 or more of the followingTemperature > 38 or < 36 oCHeart rate > 90 bpmRespiratory rate > 20/min or pCO2 < 4.2 kPaWBC > 12000/mm3 or < 4000/mm3 or > 10% bands SepsisSystemic response to infectionSIRS + infectionSevere sepsisSepsis + organ dysfunction, hypotension or hypoperfusionMay be oliguria, encephalopathy or lactate riseSeptic shockSepsis induced SBP < 90 mmHg or SBP fall > 40 mmHgPLUS hypoperfusion despite adequate fluid resuscitationi.e. sepsis-induced hypotension requiring vasopressors

67. Principles of septic shock managementINFOInitial resuscitationFluid resuscitation - ? EGDT (Rivers)DiagnosisAntibiotic therapySource identification and controlHaemodynamic and adjunctive therapyVasopressors and/or inotropes (know characteristics & pros and cons)Steroids (know relative adrenal insufficiency principles)rhAPC (know trials and controversies)Other supportBlood productsSafe ventilation in ALI/ARDS (know ARDSNet etc.)Sedation (know sedation breaks)Glucose control (know controversies medical v surgical pts)RRTDVT prophylaxisStress ulcer prophylaxis (relationship to Cdiff?)Limitation of therapy?

68. When septic shock isn’t just septic…INFOTOXIC SHOCK SYNDROMEToxins act as “superantigens”Activate up to 30% of neutrophils (normal <0.1%)Cytokine storm => MSOFDifferences in treatment from “simple” septic shockProdromal illness…source can be subtle => LOOK HARDRemember vaginal infectionsPredominant organismsS. aureus (often blood culture negative)Menstrual and non-menstrual formsMay not have protective antibodiesGroup A strep (majority blood culture positive)Therapeutic principlesAs for septic shock BUTToxin suppressing antimicrobial: clindamycin or linezolidImmunoglobulin 1g/kg then 0.5 g/kg for 4-5 days

69. Q: Nutrition - how and why?Your patient stabilises over the next 18-24 hoursShe weighs 60 kg at baselineShe hasn’t eaten at home for 5 daysHow are you going to support her nutrition?What are her requirements?How much do you give her today?How do you manage “intolerance”Why is nutrition important?

70. INFONutrition Support/TherapyWhen to feed = EARLY (< 36 hours) if possibleSupport EN with TPN but EN preferredEarly nutrition decreases infection, hospital LOS and may decrease mortalityCUMULATIVE ENERGY DEFICIT KILLS!!!!> 10000 kcal deficit correlates with poor outcome= 5 days off food in sepsis!!every day in ICU without feeding is a day closer to death!

71. INFONutrition Support/TherapyNutrition modulates stress responseNutrition modulates systemic immunityGut surface area = tennis court!!Exposure to and in harmony with trillions of organismsGALT = gut associated lymphoid tissue - appropriate exposure enhances systemic immunity

72. INFONutrition Support/TherapyNo feeding + systemic illness = leaky gut (BAD)Antibiotics = higher pH and less anaerobic flora (BAD)Anaerobes produce substances which enhance immune response (GOOD)Fewer anaerobes = poor WBC function and more systemic infection (BAD)Leaky gut = bugs and cytokines (BAD)GUT-LUNG conduit: bugs/cytokines via thoracic duct and heart to pulmonary capillary bed => lung inflammation (BAD)

73. INFONutrition Support/TherapyShort-chain fatty acids related to anaerobe levels

74. Short-chain fatty acids are colonocyte fuel

75. WBCs have receptors for SCFA = imprived function!

76. Attention to nutrition/antibiotics and pre/probioticsINFOWhat and how much?Energy (kcal)generally 25 kcal, up to 35 kcal/kgstart at 25-35% of requirement if refeeding syndrome riskProteingenerally 1.25 g/kgno need for < 1g/kg in acute liver diseaseLipids? omega-3 FA’s in ARDS (favour anti-inflammatory eicosanoids)Trace elementsselenium in sepsis?Amino acidsarginine (vasodilatory)glutamine (enterocyte fuel and ? better WBC function in trauma)

77. INFO

78. INFO

79. INFO

80. INFO

81. INFO

82. INFO

83. INFO

84. www.criticalcarenutrition.com

85. Fluid Balance & OutcomeIt’s not IF they should be dry... it’s WHEN