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Fever in the Neuro-ICU: A Deleterious and Avoidable Secondary Insult?

Fever in the Neuro-ICU: A Deleterious and Avoidable Secondary Insult?. Stephan A Mayer, MD Neurological Intensive Care Unit Columbia-Presbyterian Medical Center New York, NY. Fever Control in the Neuro-ICU. Scope of the Problem Rationale: Experimental Evidence

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Fever in the Neuro-ICU: A Deleterious and Avoidable Secondary Insult?

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  1. Fever in the Neuro-ICU: A Deleterious and Avoidable Secondary Insult? Stephan A Mayer, MD Neurological Intensive Care Unit Columbia-Presbyterian Medical Center New York, NY

  2. Fever Control in the Neuro-ICU • Scope of the Problem • Rationale: Experimental Evidence • Rationale: Clinical Evidence • Intervention: Clinical Trials • Real World: Management Strategies

  3. Fever in the Neuro-ICU Scope of the Problem

  4. Fever in the Neuro-ICU:Scope of the Problem • Hyperthermia in the Neurosurgical ICU Kilpatrick et al, Neurosurgery 2000;47:850 • 6 month study of 498 ICU admissions • Fever (38.5° C) occurred in 47% of patients • Main risk factor: ICU LOS • Minor RF: Cerebral (vs spinal) pathology

  5. Fever in the Neuro-ICU:Scope of the Problem • Potentially Detrimental Temperature Alterations in Patients at Risk for Brain InjuryAlbrecht et al, Mayo Clin Proc 1998;73:629 • Retrospective convenience sample of 120 patients • Fever was frequent and prolonged • Cardiac Arrest: 83% (35% of the time) • SAH: 70% (18% of the time) • TBI: 68% (44% of the time)

  6. Fever in the Neuro-ICU:Scope of the Problem • Risk Factors for Fever in the Neuro-ICU Commichau et al, Neurology 2003 • 4 month study of 387 neuro-ICU pts • Fever (≥38.3° C) occurred in 23% • Risk factors: Length of stay & coma • Infectious fever: Intubation • Unexplained (central?) fever: EVD • SAH only diagnosis with increased risk of both fever types after controlling for these risk factors

  7. Fever in the Neuro-ICU Experimental Evidence

  8. Rationale:Experimental Evidence • Combating Hyperthermia in Acute StrokeGinsberg et al, Stroke 1998;29:529 • “Strikingly persistent and persuasive evidence has accrued demonstrating that moderate hyperthermia during or after brain ischemia or trauma markedly exacerbates neural injury”

  9. Rationale:Experimental Evidence • Combating Hyperthermia in Acute StrokeGinsberg et al, Stroke 1998;29:529 • “This body of evidence is so overwhelming as to compel… physicians…to vigilantly monitor their acutely brain injured patients for incipient fever and maintain core temperature at normothermic levels levels for several days after (injury)”

  10. Rationale:Experimental Evidence • Deleterious effects of hyperthermia • Apply to focal and global ischemia, as well as trauma • Occur with delayed as well as acute hyperthermia • Effect is more pronounced after reversible (rather than permanent) ischemia • Causes aggravation post-ischemic brain edema as well as cellular injury • Occur even with small elevations of temperature (1-2° C)

  11. Fever in the Neuro-ICU Clinical Evidence

  12. Fever-related Brain Injury in the Neuro-ICU • Cerebral Infarction • Elevated temperature is associated with poor outcome after stroke (Meta-analysis) Hajat et al, Stroke 2000;31:410 • Subarachnoid Hemorrhage • Fever burden independently associated with mortality & poor functional outcome. Fernandez, et al, Neurology 2007;68:1013 • Intracerebral Hemorrhage • Duration of fever (>37.5° C) within the first 72 hours is independently associated with poor outcome Schwarz et al, Neurology 2000;54:354

  13. Rationale:Clinical Evidence • Intracranial Pressure Rossi et al, JNNP 2001;71:448 • 20 patients with ICP and brain temperature monitors • 10 TBI, 8 SAH, 2 neoplasm • Increases in brain temperature were associated with significant increases in ICP • Also associated with decreased AVDO2,suggesting increased CBF and CBV (exceeding CMRO2) Afebrile Febrile

  14. Elevated body temperature independently contributes to increased length of stay in neurologic intensive care unit patientsDiringer et al, CCM 2004;32;1489. • 4,295 patients admitted to a neuro-ICU with LOS >1 day • Elevated body temperature was associated with a dose-dependent • Longer ICU and hospital length of stay • Higher mortality rate • Worse hospital disposition • ICU LOS was predicted by the number of complications and elevated body temperature • The presence of elevated body temperature was associated with 3.2 additional ICU days and 4.3 additional hospital days.

  15. Fever in the Neuro-ICU Clinical Trials

  16. What About NSAIDS? Comparison of 3 treatments for fever in 75 acute stroke patients: Acetaminophen (6000 mg/d) Ibuprofen (2400 mg/d) Placebo Acetaminophen • Reduced Temp ~0.4 °C over 24 hrs • No better than placebo over 5 days of treatment van Breda EJ. BMC Cardiovascular Disorders 2005, 5:24

  17. Cold saline for Fever Control in Neuro-ICU Patients • Case series of cooling blanket + 30 cc/kg 4°C NaCl bolus • Reduction in temperature: • Pre: 39.2 ± 1.3°C • Post: 37.1 ± 1.2 °C • Reduction in fever burden 12 hours post-bolus • Not a sustainable therapy P = 0.006 Badjatia N, et al. Neurology 2006; 66:1739-41

  18. Local Cooling for Fever Control in Neuro-ICU Patients? • 19 episodes of refractory fever in 6 patients • Intervention: SubZero head and neck cooling wraps • Mild brain thermopooling noted (~0.2 °C) • Reductoions in brain temp were associated with isdentical reductions in core temp Gaida BJ, et al, EuroNeuro 2008

  19. Clinical Trial of an Air-Circulating Cooling Blanket for Fever Control in Neuro-ICU PatientsMayer et al, Neurology 2001;56:292 • 220 consecutively febrile Neuro-ICU patients • Patients randomly assigned to one of two treatment arms: • Acetaminophen 650 mg Q4H • Acetaminophen 650 mg Q4H plus air-blanket therapy (Polar Air ™ Model 600 Air Cooling System • Temperature recorded hourly for 24 hours • Treatment success: First temp ≤ 37.2˚C • Treatment failure: Two consecutive temps ≥ 38.3˚C

  20. TIME TO FAILURE TIME TO SUCCESS 9%morelikely to experience treatment success (P=NS) 12%lesslikely to experience treatment failure (P=NS) Over one-third of pts in both groups immediately exited as “treatment failures”

  21. Intravascular heat exchange catheter designed for insertion in the jugular vein and combined central venous capabilities (multiple infusion ports) Heat exchange 3 infusion lumens Outflow Inflow

  22. Treatment of fever in the neurologic intensive care unit with a catheter-based heat exchange system Diringer MN, CCM 2204;32:559 • 296 patients with T ≥38° C for at least 2 occasions • SAH, TBI, ICH and cerebral infarction • Alsius Cool Line endovascular heat exchange catheter plus standard surface cooling • Fever Burden >38 °C • 7.92 °C-hours • 2.87 °C-hours • Shivering “of concern” in four patients (3.7%) 64% relative reduction (P<0.01)

  23. Treatment of fever in the neurologic intensive care unit with a catheter-based heat exchange system Diringer MN, CCM 2204;32:559 • 296 patients with T ≥38° C for at least 2 occasions • SAH, TBI, ICH and cerebral infarction • Alsius Cool Line endovascular heat exchange catheter plus standard surface cooling • Fever Burden >38 °C • 7.92 °C-hours • 2.87 °C-hours • Shivering “of concern” in four patients (3.7%) 64% relative reduction (P<0.01)

  24. Arctic Sun: HYDROGEL LINED PADS • Arctic Sun ™ Temperature Management System • Circulates cooled water through single-use “energy transfer pads” -- lined with a layer of hydrogel -- applied directly to the body

  25. Clinical Trial of a Novel Surface Cooling System for Fever Control in Neurocritical Care Patients Mayer, et al, Crit Care Med 2004 • 47 patients with T ≥38.3° C for >2 consecutive hours after receiving acetaminophen • Median GCS 8.0 • SAH, ICH, infarction, TBI • Mean 42 hours >38.3° C prior to randomization • Interventions • Standard SubZero cooling blanket • Medivance Artcic Sun surface cooling system • Main outcome measure • 24 hour fever burden

  26. Clinical Trial of a Novel Surface Cooling System for Fever Control in Neurocritical Care Patients

  27. Predictors and clinical implications of shivering during therapeutic normothermia Badjatia N, et al, Neurocritical Care. 6(3):186-91, 2007. • 47 febrile NICU pts randomized to SubZero or Arctic Sun • 39% shivered, all but 1 in Arctic Sun group • Shivering more common in • Men (67% vs 21%, P-0.03) • Hyponatremia (44% vs 7%, P=0.03) • Hypomagnesemia (56% vs 7%, P=0.02) • Shivering was associated with increased HR, RR, and heat energy transfer (Kcal/hr) • Non-shivering patients showed greater increases in GCS at 24 hours (P = 0.02), despite receiving a similar amount of IV sedation

  28. Change in Glasgow Coma Scale

  29. IMPACT OF FEVER OF LEVEL OF CONSCIOUSNESS

  30. Fever in the Neuro-ICU Management Strategies

  31. If No Fever, How Do You Diagnose Infection? Infectious disease risks: • Pneumonia, UTI, wound infections most common in Neuro-ICU setting Monitoring • Surveillance cultures • 20% increase in baseline WBC • Track work of machine (e.g. water temp) • >20 °C indicates no minimal active cooling • <10 °C indicates intense active cooling Risk of infection may increase in setting of poor shiver control

  32. Therapeutic Normothermia: Anti-Shivering Protocol GOAL: BSAS < 1 • All Patients • Acetaminophen 1000 mg po Q6H • Buspirone 30 po q8H • Counterwarming (BAIR Hugger 43) • STEP 1: Persistent shivering • Non – sedating • MgSO4: 0.5 – 1.0 g/hr (goal: 3 – 4 mg/ dL) • Sedating • Meperidine 25-100 mg Q4h ( or 0.5 -1.0 mg/kg/hr) • Dexmedetomidine: 0.2 – 1.5 µg/kg/hr • Fentanyl 50-200 µg/hr • STEP 2: Refractory shivering • Propofol 75-300 mg/hr • Paralytics? Never for fever control!

  33. Shivering: Skin Counterwarming • Shivering • Arctic Sun 39% (9/23) • SubZero 8% (1/24) • Skin counterwarming (hands, feet, face, body) alone suppressed shivering without need for phramacologic intervention in 5 / 9 Arctic Sun patients who shivered

  34. Effect of Bair Hugger Skin Counter-warming on Systemic Metabolism in Neurocritical Care Patients Badjatia et al, in preparation Shivering at Baseline (BSAS 2-3) Not Shivering at Baseline (BSAS 0-1)

  35. Factors that Enhance the Increase in Shivering after Temporary Discontinuation of Skin Counterwarming • Moderate-to-Severe Shivering at baseline • P=0.04 • Use of IV infusion sedation at baseline • P=0.03 • Lower Mg++ levels • P=0.01

  36. Bedside Shivering Assessment Scale (BSAS) 0No shivering 1 Mild shivering localized to the neck and/or chest 2 Shivering involving neck and/or chest and arms 3 Intermittent generalized shivering involving all 4 extremities Palpate masster, pectoralis, deltoids and quadriceps muscles

  37. Concept: “Temperature Clamp” to Normothermia • Indications • Large Cerebral Infarction • SAH • ICH • Severe TBI • Goal #1: Demonstrate feasibility • Goal #2: Refine methodology (shivering) • Goal #3: Demonstrate effect on clinical outcome

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