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 FRCA Dr. Andrew Ferguson

2. Why ICU matters for the FRCA… 20 specific questions in MCQ Helps with medicine/surgery MCQs SAQs - 1 or 2 questions for sure…maybe more SOE 1 - potential topic/part of topic SOE 2 - 10 minutes of pure fun!

3. Be calm… The examiners are human (honestly!!!) The questions are (mostly) mainstream You will have seen many of the cases Guillain-Barre / Myasthenic crisis / weakness Brainstem death Status epilepticus and asthmaticus Trauma Septic shock ARDS Acute pancreatitis Burns Some 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 2008 Don’t assume you know enough…make sure you do Structure…structure…structure! Don’t waffle - answer the actual question, not the one you wanted to be asked!!

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

16. Case scenario 1 49 year old female, history of depression & anxiety found unconscious in apartment having failed to turn up for work On arrival A&E GCS 5-6, BM = 0.4 After 50ml 50% glucose BM = 14.5 and GCS 12-14 Bruising left buttock and thigh Tender abdomen, jaundiced, BP 75/45, HR 104, Temp 34.1 CT brain NAD, CT abdo - mild hepatomegaly, ? fatty Labs: 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 discussion What 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. INFO Acute 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: 179-188 Early death despite support Survival with supportive therapy (liver regeneration) Unlikely to survive with supportive therapy alone candidate for emergency transplant NOT candidate for emergency transplant

19. INFO Aetiology based therapy

20. INFO Paracetamol toxicity Major paths Enhanced risk Excessalcohol Enzyme-inducing drugs carbamazepine phenytoin, phenobarbitone St John's Wort rifampicin 3. Glutathione depletion malnutrition eating disorders malabsorption HIV Minor path NAPQI

21. N-acetylcysteine INFO (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. INFO Paracetamol Referral criteria Non-paracetamol

23. INFO Non-paracetamol Paracetamol Referral criteria - Kings College Hospital

24. Clinical Issues in ALF INFO CNS Encephalopathy - ammonia => glutamate Intracranial hypertension - oedema Cardiovascular Intravascular volume depletion Vasodilatation Subclinical myocardial damage (Tn > 0.1 in 66%) Respiratory Hypoxia - effusions, atelectasis, shunting, splinting, ALI

25. Clinical Issues in ALF INFO Renal Oliguria Acute renal impairment - drugs, hepatorenal, pre-renal, ATN, intra-abdominal hypertension Haematological Thrombocytopaenia and coagulopathy Procedural bleeding possible Spontaneous bleeding rare Infection Monocyte (HLA-DR), complement, Kupffer cell failure Responsible for most deaths!

26. INFO Useful 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 2 56 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 hypotension On arrival ICU BP = 90/45, HR 121 SR, NA @ 0.5 mg/kg/min, lactate 5 CVP 14, pO2 11 on 70% O2with PEEP 5, creps bilaterally ECG: infero-lateral ST depression In theatre 4 L crystalloid, 2 L tetraspan, 6 packed cells, 2 FFP Abdomen distended and tense, skin clammy Over next 4 hours: NA increasing, lactate 8, U/O poor Labs: 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 discussion List the main clinical issues in this case How 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?

30. Incidence

31. Aetiology

32. Pathophysiology

34. Impaired tissue perfusion

36. Systolic blood pressure < 90 mm Hg

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

38. Urine output < 20 ml/hr

40. INFO Echo indicators of mortality

41. INFO Pathophysiology

43. Incidence

44. Aetiology

45. Pathophysiology

47. INFO Therapy- Reducing iNOS Effect 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”

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

59. INFO Intra-abdominal pressure Abdominal perfusion pressure = MAP - IAP (aim > 60 mmHg)

60. INFO Abdominal CompartmentSyndrome ACS = sustained IAP > 20 mmHg (with or without APP < 60 mmHg) that is associated with new organ dysfunction/failure World Society of the Abdominal Compartment Syndrome (www.wsacs.org)

61. INFO

62. INFO

63. Case scenario 3 25 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 hypotension Intubated in A&E as hypoxic and combative, received 3 L saline On 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 bilaterally Temperature 39.7, flushed Over next 2 hours: NA increasing, lactate 9, U/O poor Labs: 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 discussion What is the differential diagnosis? What are the possible sources? What are the principles of management? Describe your haemodynamic targets and approach How 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… INFO SIRS - 2 or more of the following Temperature > 38 or < 36 oC Heart rate > 90 bpm Respiratory rate > 20/min or pCO2 < 4.2 kPa WBC > 12000/mm3 or < 4000/mm3 or > 10% bands Sepsis Systemic response to infection SIRS + infection Severe sepsis Sepsis + organ dysfunction, hypotension or hypoperfusion May be oliguria, encephalopathy or lactate rise Septic shock Sepsis induced SBP < 90 mmHg or SBP fall > 40 mmHg PLUS hypoperfusion despite adequate fluid resuscitation i.e. sepsis-induced hypotension requiring vasopressors

67. Principles of septic shock management INFO Initial resuscitation Fluid resuscitation - ? EGDT (Rivers) Diagnosis Antibiotic therapy Source identification and control Haemodynamic and adjunctive therapy Vasopressors and/or inotropes (know characteristics & pros and cons) Steroids (know relative adrenal insufficiency principles) rhAPC (know trials and controversies) Other support Blood products Safe ventilation in ALI/ARDS (know ARDSNet etc.) Sedation (know sedation breaks) Glucose control (know controversies medical v surgical pts) RRT DVT prophylaxis Stress ulcer prophylaxis (relationship to Cdiff?) Limitation of therapy?

68. When septic shock isn’t just septic… INFO TOXIC SHOCK SYNDROME Toxins act as “superantigens” Activate up to 30% of neutrophils (normal <0.1%) Cytokine storm => MSOF Differences in treatment from “simple” septic shock Prodromal illness…source can be subtle => LOOK HARD Remember vaginal infections Predominant organisms S. aureus (often blood culture negative) Menstrual and non-menstrual forms May not have protective antibodies Group A strep (majority blood culture positive) Therapeutic principles As for septic shock BUT Toxin suppressing antimicrobial: clindamycin or linezolid Immunoglobulin 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 hours She weighs 60 kg at baseline She hasn’t eaten at home for 5 days How 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. INFO Nutrition Support/Therapy When to feed = EARLY (< 36 hours) if possible Support EN with TPN but EN preferred Early nutrition decreases infection, hospital LOS and may decrease mortality CUMULATIVE 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. INFO Nutrition Support/Therapy Nutrition modulates stress response Nutrition modulates systemic immunity Gut surface area = tennis court!! Exposure to and in harmony with trillions of organisms GALT = gut associated lymphoid tissue - appropriate exposure enhances systemic immunity

72. INFO Nutrition Support/Therapy No 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)

74. Short-chain fatty acids are colonocyte fuel

75. WBCs have receptors for SCFA = imprived function!

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