WHAT IS SHOCK AND HOW COMMON IS IT IN THE ICU?

1. WHAT IS SHOCK AND HOW COMMON IS IT IN THE ICU? Jason D. Christie, MD, MSCE Assistant Professor of Medicine Assistant Professor of Epidemiology Division of Pulmonary, Allergy, and Critical Care Center for Clinical Epidemiology and Biostatistics University of Pennsylvania, Philadelphia, USA

3. Roadmap • Definition of Shock • Global Definition of Shock • Epidemiological Considerations of Operational Definitions • Specific Definitions of Shock • Sepsis • Cardiogenic • Other • Incidence of Different forms of Shock • Sepsis • Cardiogenic • Other

4. Global Definition of Shock • “A state of profound depression of the vital processes associated with reduced blood volume and pressure and caused usually by severe especially crushing injuries, hemorrhage, or burns.” • Merriam-Webster Dictionary • Alternative definitions: • “a violent shake or jar,” • “disturbance in the equilibrium or permanence of something.” • Etymology • Middle French choc, from choquer “to strike against” • Middle Dutch schocken “to jolt.”

5. “Shock” Definition in Critical Illness • Useful to categorize of shock as • Cardiogenic • Distributive • Septic • Anaphylactic • Hypovolemic • These groups have been studied separately by researchers from each discipline

6. Global “Shock” Definition • The Global definition of shock has remained relatively consistent in clinical studies, and generally includes: • “Persistence of arterial hypotension despite adequate volume resuscitation” • Definition forms most of the clinical research on incidence of the various forms of shock

7. CCEB Shock Definition • Is it Valid? • Capture what you think it does?

8. CCEB Shock Definition • Is it Valid? • Capture what you think it does? • Reliable? • Can it be reproduced? • Do different researchers call the same patients “shock”?

9. Validity of clinical criteria SBP<90 Despite adequate volume load

10. Validity of clinical criteria SBP<90 Despite adequate volume load

11. CCEB Validity of Shock Definition • Face Validity • Does it make sense • Content Validity • Have panels of experts agreed it makes sense and includes all components of “shock” • For several shock subsets, these forms of validity exist (e.g. cardiogenic and septic)

12. CCEB Validity of Shock Definition • Criterion (Gold Standard) Validity • Measured against a Gold Standard • This does not exist in Shock • “Tarnished Gold Standard”

13. CCEB Validity of Shock Definition • Criterion (Gold Standard) Validity • Measured against a Gold Standard • This does not exist in Shock • “Tarnished Gold Standard” • Discriminant “Predictive” validity • Do different forms of the definition predict mortality differently? • Construct Validity • Is the definition related to different biological physiological signals?

14. Reliability of Shock definition • Agreement between investigators: • Septic Shock • CUB-Rea study, agreement on coding of cardiovascular failure was 89% Annane, AJRCCM 2003; 168:165-72

15. Reliability and Validity of Shock Definitions • Although not perfect, some validity and reliability data exist on septic and cardiogenic shock • Studies of incidence are reasonable given these operational definitions

16. Roadmap • Definition of Shock • Global Definition of Shock • Epidemiological Considerations of Operational Definitions • Specific Definitions of Shock • Sepsis • Cardiogenic • Other • Incidence of Different forms of Shock • Sepsis • Cardiogenic • Other

17. CCEB Septic Shock Definition • Early 1990s, Bone et al. defined “septic shock”: “Sepsis with arterial hypotension, despite adequate fluid resuscitation.” • Sepsis: SIRS plus infection • Severe sepsis: sepsis with organ dysfunction. • SIRS defined as two or more of: • Temp >38°C or <36°C • HR >90 min • RR >20 min or a PaCO2 <32 mm Hg • WBC >12,000 or <4,000.

18. Septic Shock Definition • In 2001, Joint Consensus Conference: “A state of acute circulatory failure characterized by persistent arterial hypotension unexplained by other causes.” • Arterial hypotension • systolic BP <90 mm Hg • MAP <60mmHg • reduction in systolic BP of <40 mm Hg from baseline • despite adequate volume resuscitation • in the absence of other causes for hypotension Levy, CCM. 2003; 31:1250-6

19. Parasite Severe Sepsis Virus SIRS Sepsis Infection Fungus shock Trauma Severe SIRS Bacteria BSI Burns Definitions Adapted from SCCM/ACCP Consensus Guidelines

20. International Sepsis Definitions Conf. • Systemic inflammation • Concept remains valid • Specific “2 or 3 out of 4” criteria are arbitrary and unhelpful • Biomarkers may eventually be more useful • IL-6 vs. tachycardia • Recommendation • Stop using SIRS to define sepsis • Expand clinical criteria for evidence of sepsis • Consider ‘staging’ classification analogous to TNM Levy et al. Crit Care Med 2003.

21. Fever Arterial hypotension Increased CRP Increased PCT Increased SvO2 Increased cardiac output Tachycardia Arterial hypoxemia Acute oliguria Increased creatinine Coagulation abnormalities Hyperlactatemia Thrombocytopenia Decreased capillary refill or mottling Leukocytosis Leukopenia Hypothermia Ileus Altered mental status Significant edema or positive fluid balance Hyperbilirubinemia Hyperglycemia Diagnostic criteria for sepsis Infection PLUS some of the following Levy et al. Crit Care Med 2003.

22. Cardiogenic Shock Definition • Sustained systemic hypotension: • Systolic BP <90 mm Hg • MAP 30 mm Hg or more below basal levels • Adequate or elevated left ventricular filling pressures • PAOP >15 mm Hg • cardiac index <2.2 L/min/m2 • Some studies use clinical signs indicative of poor tissue perfusion • Oliguria • clouded sensorium • cool, mottled extremities Hollenberg, Ann Intern Med. 1999; 131:47-59.

23. CCEB Other Shock Definitions • Studies are less complete/consistent • Anaphylactic shock • signs of anaphylaxis • hypotension requiring urgent medical attention. • Burns, blunt and penetrating trauma • persistent hypotension, despite volume resuscitation • similar to septic shock

24. Roadmap • Definition of Shock • Global Definition of Shock • Epidemiological Considerations of Operational Definitions • Specific Definitions of Shock • Sepsis • Cardiogenic • Other • Incidence of Different forms of Shock • Sepsis • Cardiogenic • Other

25. CCEB Incidence and “Treatable shock” • Most Incidence estimates are actually for “Treatable Shock” (Linde-Zwirble, Crit Care 2004) • Subjects must be in a setting where shock criteria can be applied (hospital or ICU) • Shock and death at home or a nursing home are not counted (e.g. following sepsis or MI) • Most Incidence Estimates are expressed as “incidence of shock per ICU admissions” • Pragmatically this makes sense • Define the population we want to intervene upon • However, given the reliance on admission to the ICU, incidence estimates may vary between countries and setting, depending on the number of ICU beds and treatment decisions.

26. CCEB Incidence of Septic shock • Much of the epidemiology of sepsis has focused on severe sepsis (sepsis with the presence of organ dysfunction). • However, septic shock has been the focus of multiple large epidemiological studies. • In general, the incidence of septic shock has been relatively consistent • 6-10 per 100 ICU admissions (6-10%). • The incidence of septic shock may be increasing • affecting nearly 10% of patients during ICU stay

27. Earlier studies • Rangel-Frausto (1995) • 9 month study in surgical ICUs in Iowa • 2527 individuals with SIRS criteria. • 10 individuals developed shock • defined as a SBP<90 unresponsive to fluids. • The incidence of septic shock was estimated at 6.3 per 100 SICU admissions Rangel-Frausto JAMA 1995; 273:117-23

28. Earlier studies • Brun-Buisson 1995 • French ICU Group for Severe Sepsis • 170 adult ICUs in France • Data collected over two months • 11828 admissions • The incidence of septic shock was estimated at 6.4 per 100 ICU admissions Brun-Buisson JAMA. 1995; 274:968-74.

29. Earlier studies • Brun-Buisson 1996 • French Bacteremia Sepsis Study Group • 2345 individuals collected over 2 months • 24 hospitals France • Estimate of 8.7 per 100 ICU admissions Brun-Buisson AJRCCM 1996; 154:617-24

30. Earlier studies • Italian SEPSIS study 1995 • one year study of 99 Italian ICUs • data collected between 1993 and 1994 • 1101 subjects • The reported incidence was 6.1 per 100 ICU admissions Salvo, Intensive Care Med. 1995; 21:S244-9

31. More recent studies • CUB-Rea 2003 • 100,554 ICU admissions in France • Between 1993 and 2000. • 8,251 episodes of septic shock. • Overall incidence 8.2 per 100 admissions. • Incidence of septic shock increased from 7.0 in 1993 to 9.7 per 100 admissions in 2000 Annane AJRCCM 2003; 168:165-72

32. Incidence and Mortality Over Time Annane AJRCCM 2003; 168:165-72

33. More recent studies • EPISEPSIS 2004 • Collected data during a 2 week study period • 3738 ICU admissions were screened for severe sepsis • 621 (16.6%) were identified as having a first episode of clinically suspected severe sepsis • Of these, 58.8% had cardiovascular failure • If “cardiovascular failure” defines shock • Incidence 9.8 per 100 ICU admissions. • Extrapolating these findings to France • 0.56 per 1000 residents per year for septic shock Brun-Buisson, Intensive Care Med. 2004; 30:580-8.

34. More recent studies • Alberti 2005 • Studied the incidence and progression to septic shock among ICU admissions • May 1, 1997 and April 30, 1998 • 8 countries from Europe, Canada and Israel • 13906 individuals with complete data • Combined data from shock on presentation, with those that developed shock during hospitalization yields 1117 + 201 = 1318 individuals with shock • Incidence of septic shock for all ICU admissions was 1318/13906 or 9.5 per 100 ICU admissions. Alberti AJRCCM. 2005; 171:461-8

35. Alberti AJRCCM. 2005; 171:461-8

36. More recent studies • Brazilian Sepsis Epidemiology Study (BASES) 2004 • 4 ICUs across Brazil • 1383 subjects • Higher reported incidence than France and US Silva, Critical Care 2004

37. Silva, Critical Care 2004

38. Incidence of Septic Shock • Septic shock occurs commonly in the ICU • Incidence is rising slightly • Current estimates approach 10% of all ICU admissions having septic shock • Approximately 1 in 2000 individuals in France will get Septic Shock each year

39. CCEB Incidence of Cardiogenic Shock • The incidence of cardiogenic shock has been mostly studied in the context of occurrence of shock following acute myocardial infarction • Over the past 20 years, the incidence of shock complicating acute MI has been relatively stable between 6% and 9% • Probably underestimates cardiogenic shock from all causes • Significant proportion have overlap with sepsis

40. Studies of Cardiogenic Shock • MILIS study group 1989 • 845 patients with acute MI • In this cohort, there was an overall incidence of 7.1%. • Shock largely defined clinically • GUSTO-1 1995 • 2972 of the 41278 patients enrolled developed shock (7.2%) Hands JACC 1989; 14:40-6 Holmes JACC. 1995; 26:668-74

41. More Recent Studies • Goldberg 1999 • 9076 Worcester, Mass residents • Hospitalized with MI • 11 one-year periods between 1975 – 1997 • The incidence of cardiogenic shock remained relatively stable over this time period, averaging 7.1% of all acute MI Goldberg NEJM. 1999; 340:1162-8

42. Studies using National Registry of Myocardial Infarction (NRMI) • Goldberg 2001 • 426,253 patients in NRMI • hospitalized with MI at 1662 hospitals in USA • Data collected between 1994 and 1997. • The incidence rates of cardiogenic shock over this time period averaged 6.2%. • Slight decline in incidence rates between 1994 (6.6%) and 1997 (6.0%) Goldberg Am Heart J. 2001; 141:65-72

43. Studies using NRMI • Babaev 2005 • NRMI from 775 hospitals in USA • 1995 and 2004 • 293 633 patients with ST-elevation MI • 25 311 developed cardiogenic shock • Incidence of 8.6 per 100 ST-elevation MI Babaev JAMA. 2005; 294:448-54.

44. Babaev JAMA. 2005; 294:448-54.

45. Sepsis and Cardiogenic Shock • SHOCK Trial 2005 • 18% of subjects with cardiogenic shock had suspected sepsis as cause of shock, • indicated by leukocytosis • inappropriately low systemic vascular resistance. • Of subjects with suspected sepsis, 74% had culture-positive infection. • This and other observations have led investigators to challenge paradigms of cardiogenic shock • inappropriate vasodilatation may be involved Kohsaka Arch Intern Med. 2005; 165:1643-50

46. Anaphylactic Shock • Considerably rarer and less fatal than either septic shock or cardiogenic shock • In the USA: • 1 percent of all emergency dept visits • 500 to 1000 fatalities per year • True incidence is difficult to determine accurately because of underdiagnosis and underreporting Neugut Arch Intern Med. 2001; 161:15-21

47. Anaphylactic Shock • Yocum 1999 • Population based study in Olmsted County, MN • 1255 residents between 1983 and 1987, • 133 residents had > one episode of anaphylaxis. • estimated incidence was 21 per 100,000 person-years. Death in this cohort was very rare • Peng 2004 • General Practice Research Database in the UK • 1994-1999 675 cases of anaphylaxis • Incidence was estimated to be 8.4 per 100 000 person-years. • 10% of cases had hypotension and shock that required urgent treatment. Yocum, J Allergy Clin Immunol. 1999; 104:452-6 Peng, Arch Intern Med. 2004; 164:317-9

48. Burns, Trauma and Hemorrhage • Not as rigorously studied • Definitions difficult to apply • Most studies of trauma have focused on organ failure and mortality as outcomes

49. Burns, Trauma and Hemorrhage • Muckart 1997 • 450 critically injured patients • determine rates of septic and sterile shock following ICU admission for trauma • Majority had penetrating trauma • Incidence of septic shock was 20.2% • Sterile shock was 9.3% Muckart CCM 1997; 25:1789-95

50. Burns, Trauma and Hemorrhage:Other definitions • Schulman 2004 • Prolonged Occult Hypoperfusion (POH) • defined as serum lactate >2.4 mmol/L persisting >12 hours from admission • 378 trauma ICU patients • 129 (34.1%) developed POH during ICU stay Schulman J Trauma. 2004; 57:795-800.