Understanding Hyperthermia: Dr. Kelly Kasteel Case Study

1. That’s Hot!Dr. Kelly Kasteel Case Study-hyperthermia

2. Hyperthermia: Epidemiology • 4,000 heat related deaths yearly (US) • 80% of the fatalities are elderly • Occurs in 5 per million over age 85 compared to 1 per million in the 5-44 age group • 2nd leading cause of death among young athletes • Very young (<4yo) also at increased risk • Occurs in 0.3 per million compared to 0.05 per million in patients > 4yo.

3. Case Study-History • 36 y.o female • Admitted-SPH 11/07/2007 (73 previous visits) • Vancouver is experiencing a rare heat wave where outside temperatures have ranged between 37-39 degrees • Brought in via EHS agitated, spitting, naked and running into traffic at the scene. • Hx of ? 45 second seizure en route to the hospital which is not clearly documented. • Remote history of foul stools over the previous week before admission • Without complaint at arrival, but…had precipitous decrease in LOC and was intubated for airway protection

4. Case Study-History • PMHx 1.  Hepatitis C. 2.  BAD • Meds • None. Previously (1/12) on Risperidone-2mg qhs via pharmanet • Allergies • None • SHx • Prostitution – multiple STD’s in past • Polysubstance abuse (cocaine/heroine IVDU). • Last used this am

5. Case Study-On Examination • HR-144 reg/ RR-22/ Temp-41 C/ BP-90/40/ • Pressure support 15, PEEP of 5, FiO2 of 0.5, • CPP was 11, mixed venous 81% and a MAP of 75 with no pressor support.  • Spent 8 hrs in ED before transfer to ICU

6. Case Study-On Examination • CVS-s1s2 no murmur no s3s4 • Resp- eae no wheeze no crackles • Abdo-soft non-tender • GU – ++discharge, no FB • Neuro- Initially the ED, the pt was confused and combative with a GCS E3M5V2 = 10. Moving all 4. Pupils 3 reactive. • MSK- Injection marks over antecubital space • Derm- Warm and Dry

7. Case Study- Labs • Glucose-6.8 • Sodium-142 • Potassium-5.4 • Chloride104 • Bicarb 11 • Urea 6.3 • Creatinine 147 • Total Bili 8 • Osmolality 319 • Anion Gap-27 • CK -405 • Troponin0.19 • Amylase-1018 • TSH -0.52 • B-HCG- weakly positive • Ethalene glycol/methanol- cancelled • Tox serum screen (asa- weakly positive 0.2, acetaminophen, etoh)-negative

8. Case Study- Labs • Infectious workup • Genital C/S- Normal flora • Stool C/S – Negative • Sputum-Negative • Urine –Negative • Blood C/S- 1 bottle gram positive cocci in clusters-coag negative staphlococcus • Hypoglycemia- Glucose-0.7 (24 hrs after admission) • Hyponatremia-Sodium-128 • ARF-Creatinine-600 • APTT-189 • INR >9 (july 12) • Fibrinogen-1.0 • D- dimmer >4000 • Hepatitis-AST 1000, ALT 5573, GGT 66, BR 666(total)) • Blood smear-schistocytes, burr cells

9. Case Study-Imaging CT head- July 24th There is severe compression of structures in the fourth ventricle.   Fluid around the brainstem has been effaced and the fourth ventricle is compressed.  The patient is at risk for developing transtentorial or tonsillar herniation. Severe cerebral edema.  • CXR: small lung volumes, no obvious airspace disease

10. Case study- Course in Hospital • Treated presumptively as sepsis nyd- piptazo, flagyl • Negative workups – no identifiable septic or obstetrical causes for DIC. • July 23-24- Patient briefly extubated before re-intubation and markedly decreased LOC. • Brain Death • Comfort care initiated July 24th, patient deceased within the hour. • Autopsy- Non-contributory to date-MOS

11. Now That’s HOT • What is your differential diagnosis for this pt? • What are the potential complications that can occur in heat stroke? • What investigations should you order? • What other therapies should be considered?

12. Basic principles of Heat • 4 mechanisms that allow the body to maintain a constant core temperature • Radiation • Convection • Conduction • Evaporation

13. Fever vs. Hyperthermia • Fever • Elevation of body temp due to the “resetting” of the hypothalamic set point in response to endogenous or exogenous pyrogens • Hyperthermia • Elevation of body temp abovethe hypothalamic set point due to the failure of the body’s heat dispersing mechanisms

14. Diff Dx - Hi temp with altered mental state

15. Heat Stroke • Total breakdown of body’s thermoregulatory system • Leads to multiorgan damage if left untreated • A true medical emergency • 2 forms described • Exertional • Non-exertional/Classical

16. Exertional Heat Stroke • Occurs in young, healthy individuals engaged in heavy exercise during periods of high ambient temperature and humidity • One series of 58 patients with heat stroke found an acute mortality rate of 21 percent (Ann Intern Med 1998 Aug 1;129(3):173-81)

17. Non-exertional heat stroke • Affects individuals with underlying chronic medical conditions that either impair thermoregulation or prevent removal from a hot environment. • Conditions include: • Cardiovascular disease • Neurologic or psychiatric disorders • Obesity • Anhidrosis • Extremes of age • Anticholinergic agents or diuretics

18. Diff Dx - Hi temp with altered mental state • INFECTIOUS • Sepsis, Meningitis/Encephalitis, Falciparum malaria • DRUG/TOXIN INDUCED • Overdose – anticholinergic, sympathomimetic • Withdrawal – benzodiazepene, alcohol – delirium tremens • Neuroleptic malignant syndrome • malignant hyperthermia • Serotonin syndrome • ENDOCRINE • Thyroid storm, Pheochromocytoma • CNS • Hypothalamic hemorrhage, status epilepticus esp nonconvulsive

19. Neuroleptic Malignant Syndrome • Impaired thermoregulation in hypothalamus due to relative lack of dopamine • Caused by antipsychotic meds/neuroleptics • Distinguishing features • hyperthermia, • altered mental status • "lead pipe" muscle rigidity,choreoathetosis, tremors • autonomic dysfunction- diaphoresis, labile blood pressure, and dysrhythmias • Hx of psychotic disorder/neuroleptic medication use Treatment • Cooling, hydration, benzodiazepines • Bromocriptine, amantadine, dantrolene

20. Malignant Hyperthermia • Rare (autosomal dominant) • Genetic instability of sarcoplasmic reticulum causing massive calcium release • Onset: 1 to 10 hours after exposure • Triggered by inhalational anaesthetic or succinylcholine • Distinguishing features • History of succinylcholine use • Muscular rigidity • Treatment • Cooling, hydration • Dantrolene

21. Serotonin syndrome • Excess serotonin and dopamine levels in CNS • Triggered by any med that increases serotonin levels (eg. SSRI’s, demerol, dextromethorphan, lithium etc.) • Distinguishing features • Appropriate medication history • Muscular rigidity • Treatment • Cooling, Hydration • Cyproheptadine

22. Thyroid storm • Hypermetabolic state from extreme thyrotoxicosis • Distinguishing features • History of thyroid disease • Goiter • Ophtho clues  lid retraction/lag, exophthalmos, EOM palsy • Treatment • Cooling, Hydration • PTU, iodide solution, propranolol etc.

23. Overdose • Anticholinergics, sympathomimetics • Distinguishing features • Hx of ingestion • Toxidromes • Treatment • Cooling, hydration • Benzodiazepine, Decontamination

24. Diff Dx cont’d • The differential for heat stroke contains many potentially life threatening illnesses • It all comes down to your • ABC • Cooling • Hemodynamic support

25. Heat Stroke – Complications • CNS • Cerebral edema • Permanent neuro damage eg. cerebellar deficits, hemiplegia, or dementia is possible after severe cases • Renal • Myoglobinuric renal failure-rhabdomyolysis • Cardiopulmonary • Heart failure • Pulmonary edema

26. Heat Stroke - Complications • Electrolyte • Hypo or Hyperkalemia • Hypernatremia • Hypocalcemia, hypomagnesemia • Hematologic • Thrombocytopenia • DIC • Hepatic • Centrilobular necrosis – not permanent • However, can be a useful diagnostic adjunct

27. Heat Stroke – Hepatic Damage • “ Hepatic damage is such a consistent feature of heat stroke that its absence should cast doubt on the diagnosis “ From Rosen’s 5th edition p2003

28. Heat Stroke - Diagnostic Criteria • Classic triad • Markedly elevated temp ( >40.5 degrees ) • CNS dysfunction • Anhidrosis • Caveats • Sweating seen 50% of the time esp. in exertional heat stroke

29. Investigations • CBC+diff , blood culture Infection, thrombocytopenia • Electrolytes, ABG Electrolyte derangement, acidosis • Chemstrip/Glucose DKA • BUN, Cr Renal failure • U/A, urine for myoglobin Rhabdomyolysis • Hepatic panel Liver damage • INR, PTT, Fibrinogen etc DIC • CT Head Intracranial event, pre-LP • LP Meningitis/encephalitis • Thyroid panel Thyrotoxicosis • CXR Pulmonary Edema • EKG Secondary ischemia

30. Initial management

31. Treatment summary • The Basics… • Resusc room, oxygen, iv, monitors • Vitals-including continuous rectal temp monitoring • The ABC’s… • Airway, Breathing • Cooling • Evaporative/Immersive +/- adjuncts • Circulation • Cautious rehydration • Pressor support as needed

32. Treatment summary cont’d • More ABCDE’s…. • +/- Antibiotics ? Sepsis, meningitis • +/- Benzodiazepines ? Withdrawal syndrome • +/- Cyproheptadine ? Serotonin syndrome • +/- Dantrolene ? Malignant Hyperthermia • ? Neuroleptic Malig Syndrome • +/- Decontamination ? Ingestion • +/- Endocrinopathy tx ? Thyroid storm

33. What about antipyretics? • Acetaminophen and ASA are not indicated in heat stroke • These drugs counteract fever caused by an elevated hypothalamic set point • In heat stroke, the increased temperature is due to an entirely different mechanism • ASA --> may worsen coagulopathy • Acetaminophen --> may exacerbate hepatic damage

34. Cooling • The key to successful outcome in heat stroke • Prognosis in heat stroke is directly related to how quickly the body can be cooled down • Goal is to cool by 0.1-0.2 degrees/min

35. In the ER ….Cooling Methods • Immersion • Evaporation

36. Ice Water Immersion • Primary cooling mech = conduction • Pt is undressed and placed into a tub of ice water deep enough to cover the trunk and extremities • Can achieve cooling rates of 0.13 degrees/min • Can decrease core temp to 39 degrees in 10-40 min

37. Ice Water Bath-Disadvantages • Can’t perform defibrillation or resuscitative procedures while immersed • Vasoconstriction  Shunting of blood from the skin  ? Heat exchange • Induced shivering  endogenous heat production • Uncomfortable

38. Evaporative Cooling • Fans positioned beside an undressed pt while warm water is sprayed/sponged on • Pt kept continually wet for continued cooling • Can achieve cooling rates comparable to immersive techniques

39. Evaporative Cooling-Advantages • Easier patient access • No induced peripheral vasoconstriction • Less induced shivering • More comfortable for the patient

40. Methods of Cooling • Br J Sports Med 2005 Aug;39(8):503-7 • Review of 17 journal articles. • Modalities of reducing body core temperature in patients with exertional heatstroke • The most effective method is immersion in iced water • The practicalities of this treatment may limit its use

41. Cooling Goal • Keep rectal temperature <39.4ºC and skin temperature 30ºC-33ºC. • Cooling should be discontinued when rectal temp hits 39-40 degrees • to avoid “overshoot” hypothermia • Avoid: • antipyretic agents • Alcohol sponge baths • Alpha-adrenergic agonists

42. Main Predictors of Outcome • Duration and degree of hyperthermia • Time to cooling • Indicators of organ dysfunction, such as transaminases, LDH and CK

43. Cooling methods cont’d • To counteract shivering… • Benzodiazepines • Phenothiazines – advocated in the past, however may potentially lower seizure threshold • If severe- non-depolarizing paralytic

44. Circulation – Main Issues • Hypotension and dehydration are the main issues for heat stroke patients • Usually, more than one cause for hypotension • Hypovolemia • Increased peripheral vasodilatation

45. Circulation – Complicating factors • Heat stroke patients are at high risk of developing pulmonary edema and renal failure • Cooling a patient will redistribute peripheral blood flow back to the core • Need careful balance between hydration and preventing fluid overload

46. Circulation-Approach to hypotension • 1st line – cooling • Will redistribute volume from periphery to core • 2nd line – judicious hydration • Most sources suggest 250-500 cc/h • Titrate to hemodynamic response, urine output, age and PMHx of patient etc. • Invasive monitoring may be indicated for complicated cases

47. Circulation-Approach to hypotension • 3rd line – pressors • Be cautious with primarily alpha blocking agents (eg. Levophed) • Will cause further vasoconstriction and could potentially decrease heat exchange • No definitive evidence on which pressor is the “best” to use

48. Heat exhaustion vs Heat stroke • Important to think of heat exhaustion and heat stroke as two ends of a spectrum • The point at which heat exhaustion becomes heat stroke --> when thermoregulatory mechanisms fail or are overwhelmed • Heat exhaustion can easily progress to heat stroke if not adequately treated • Thus early recognition and treatment essential!

49. Heat exhaustion vs. Heat stroke - Differentiation • Vital signs • In general, heat exhaustion < 40 deg, heat stroke > 40 deg • Remember though that prehospital cooling may have occurred in the heat stroke patient • Clinical exam • Heat stroke implies significant CNS dysfunction – seizures, coma, very altered mental state • Pts with heat exhaustion have less florid CNS dysfunction- eg. mild disorientation, clumsiness

50. Heat exhaustion vs. Heat stroke-Bottom line • If the possibility of heat stroke is entering your mind, initiate immediate tx (ie Airway, Breathing, Cooling, Diff Dx) • Hepatic transaminases may be a useful differentiating factor – but you must initiate immediate cooling while you wait for results