National Best Practices in Care of Traumatic Brain Injury

National Guidelines and Best Practices in Care of TBI

Maziyar A. Kalani MD Mayo Clinic Arizona Phoenix, AZ

• Understanding Physiologic Thresholds in Managing Traumatic Brain Injury

• National Best Practices

©2019 MFMER | slide-3 Head Elevation Head Elevation • Reduces ICP by increasing venous return • May temporarily help shift increased CSF out into the venous system Monro-Kelli Doctrine Ventilation Therapies

Level IIB

• Prolonged prophylactic hyperventilation with PaCO2 of 25 mm Hg or less is not recommended.

Previous Standard

• Hyperventilation is recommended as a temporizing measure for the reduction of elevated intracranial pressure (ICP). • Hyperventilation should be avoided during the first 24 hours after injury when cerebral blood flow (CBF) is often critically reduced.

• If hyperventilation is used, jugular venous oxygen saturation (SjO2) or brain tissue O2 partial pressure (BtpO2) measurements are recommended to monitor oxygen delivery.

Monro-Kelli Doctrine Pharmacologic Management of ICP

Steroids Pharmacologic Management of ICP Pharmacologic Management of ICP Pharmacologic Management of ICP

IC Oxygenation Inflammatory Hemodynamic Volume P Response Benefit Limit Mannitol  / /  No HTS     Yes Pharmacologic Management of ICP

Level IIB

• Mannitol is effective for control of raised intracranial pressure (ICP) at doses of 0.25 g/kg to 1 g/kg body weight. • Arterial hypotension (systolic blood pressure <90 mm Hg) should be avoided. Monro-Kelli Doctrine Decompressive Craniectomy (DC)

Level IIA

• Bifrontal DC • Does not improve GOS-E score at 6 months without mass lesions • Can reduce ICP and thus minimize ICU days • Large frontotemporoparietal DC • Does reduce mortality in severe TBI • No smaller than 12 x 15 cm or 15 cm diameter Surgical Decompression

• Trauma flap reverse “?” mark • Low temporal bur hole • Large craniotomy >15 cm • Resection of temporal bone • Stellate dural opening • Use of gel film to facilitate cranioplasty • Placement of contralateral ICP monitor if indicated Surgical Decompression

• DECRA Trial • Unchanged mortality with DC (19% vs. 18%) • Worse disability outcome with DC • Bifrontal Craniotomy had suboptimal outcomes

• RESCUEicp Trial • Improved mortality with DC (27% vs. 49%) • Worse disability outcome with DC • Early hypothermia no longer recommended

• DC does not improve outcomes, only survival Surgical Decompression Surgical Decompression Monro-Kelli Doctrine

Intracranial Pressure (ICP) Monitoring Level IIB

• ICP monitoring in severe TBI reduces in-hospital and 2- week post-injury mortality.

No Evidence

• ICP should be monitored in all salvageable patients with a severe TBI and an abnormal CT scan. • ICP monitoring is indicated in patients with severe TBI with a normal CT scan if two or more of the following features are noted at admission: age over 40 years, unilateral or bilateral motor posturing, or systolic blood pressure (BP) <90 mm Hg.

23 Cerebrospinal Fluid Drainage

Level III • An EVD system zeroed at the midbrain with continuous drainage of CSF may be considered to lower ICP burden more effectively than intermittent use. • Use of CSF drainage to lower ICP in patients with an initial GCS <6 during the first 12 hours after injury may be considered Level IIB • Treating ICP above 22 mm Hg is recommended • >22 mmHg are associated with increased mortality Beyond Intracranial Pressure

• Cerebral Perfusion Pressure

CPP = MAP – ICP

• ΔICP will ΔCPP • Hypotension detrimental • CBV affects ICP

26 Cerebral Perfusion Pressure Monitoring

Level IIB • CPP -based management of severe TBI decreases 2-week mortality • Maintaining CPP between 60-70 provides favorable outcomes Level III • Maintaining SBP at ≥100 mm Hg for patients 50-69 years old or • Maintaining SBP ≥110 mm Hg or above for patients 15-49 or >70 years old decreases mortality and improve outcomes. • Avoid aggressive attempts to maintain CPP above 70 mm Hg with fluids and pressors du to the risk of adult respiratory failure.

27 Seizure Prophylaxis

• Post -traumatic seizures occur in approximately 25% of victims of head injury • Highest rate within 7-10 days of injury

Level IIA • Prophylactic use of phenytoin or valproate is not recommended for preventing late posttraumatic seizures (PTS) • Phenytoin is recommended to decrease the incidence of early PTS (within 7 days of injury), when the overall benefit is felt to outweigh the complications associated with such treatment. However, early PTS have not been associated with worse outcomes. Cheat Sheet of Best Practices

• Level I • Avoid Steroids • Level IIA • Frontotemporoparietal Decompressive Craniectomy >15cm in diameter improves survival • Bifrontal Decompressive Craniectomy helps with ICP but not outcome • Start feeds no later than 7 days of injury • Consider early tracheostomy • Phenytoin reduces 1 week post-injury seizure risk Cheat Sheet cont.

• Level IIB • Keeping ICP below 22 reduces in-hospital and 2 week mortality • CPP management to 60-70 improves outcome • Prolonged prophylactic hyperventilation is not recommended • Early, short term prophylactic hypothermia is not recommended • Consider barbituates or propofol for refractory ICP management but not burst suppression • GJ tube reduces incidence of pneumonia Cheat Sheet cont.

• Level III • CSF drainage may be considered • Use antibiotic-impregnated catheters • LMWH or Unfractionated Heparin with Mechanical DVT Prophylaxis • Consider advanced cerebral monitoring with jugular saturation above 50% • Keep SBP above 100 for adults and above 110 for younger and older patients • Avoid pulmonary complications related to keeping CPP above 70 • Put it all together: ICP, clinical and imaging data Next Frontier

• Thinking beyond ICP management • Maximizing oxygenation without increasing secondary injury • Balanced cerebral metabolism • Management of secondary systemic complications Thank you

10 new studies; 4 from prior edition • One Class 1 and four Class 2 support recommendations • Nine Class 3 included as lower level of evidence

Study Number Quality of Topic of Studies Evidence OVERALL QUALITY – Class 1 and 2 Use of ICP monitor information to guide 1 RCT Low treatment 4 Cohorts

40 Intracranial Pressure Monitoring Evidence Supporting Recommendations

STUDY RESULTS CONCLUSION

Use of ICP monitor information to guide treatment

Alali, 2013* • Mortality: Adjusted OR 0.44; • Patient-level: ICP Cohort; Class 2; p<.0001 monitoring associated with n=10,628 • Association of ICP monitoring lower mortality Relationship between and lower mortality more • Hospital-level: variability in ICP monitoring and pronounced in patients under ICP monitoring explained mortality 65 small part of variability in mortality Chesnut, 2012* • Mortality at 6 months: 39% vs • Did not support the RCT; Class 1; n=324 41%; p=.6 hypothesized superiority ICP monitoring vs • GOS-E at 6 months: Favorable of ICP monitoring over imaging and clinical outcome 44% vs 39%; p=.4 clinical assessment in exam this environment

41 Intracranial Pressure Monitoring Evidence Supporting Recommendations (continued) STUDY RESULTS CONCLUSION

Use of ICP monitor information to guide treatment

Farahvar, 2012* • Mortality 2-weeks • Patients managed based Cohort; Class 2; • Adults only OR 0.64; p=.05 on ICP monitoring have n=1307 • All ages OR .63; p=0.2 lower risk of 2-week ICP monitoring or not in mortality patients treated for ICH Gerber, 2013* • 2001-9 Age adjusted • Significant decrease in Cohort; Class 2; mortality/compliance ICP mortality appears to be n=2320 monitoring associated with increase in Mortality and guideline • 01-03 22.4% / 55.6% adherence to guidelines adherence trends • 04-06 19.7% / 72.3% • 07-09 13.3% / 75.2% Talving, 2013* • Mortality: adjusted OR (no ICP • ICP Monitoring reduces Cohort; Class 2; n=216 monitoring is referenced) OR mortality but increases Patients with and 0.15; p=.019 ICU and Hospital LOS without ICP Monitoring • Longer LOS with and without deaths

42 Prophylactic Hypothermia Evidence Overview

9 new studies; 6 from prior edition • One Class 1 and six Class 2 support recommendations • Six new Class 3 included as lower level of evidence • Two new studies add new topics but provide insufficient evidence for recommendations Study Number Quality of Topic of Studies Evidence OVERALL QUALITY – Class 1 and 2 Hypothermia vs normothermia 7 RCTs Low

Short term vs long term cooling 1 RCT Insufficient

Head vs systemic cooling 1 RCT Insufficient

43 Prophylactic Hypothermia Evidence Supporting Recommendations STUDY RESULTS CONCLUSION

Hypothermia vs Normothermia

Clifton, 2011* • Mortality: RR 1.30; p=.52 • Trial stopped for futility RCT; Class 1; n=97 • Poor outcomes: RR1.08; p=.67 • No significant difference 48 hours of early • Complications: no difference in outcomes hypothermia Aibiki, 2000 • Mortality: 6.7% vs 27.3% • Better outcomes with RCT; Class 2; n=26 • Mean GOS at 6 months 4.2 vs hypothermia Moderate hypothermia 2.9; p=.04 3-4 days Clifton, 1993 • Mortality: 35% vs 36% • No difference in RCT; Class 2; n=46 • GOS at 3 months % good outcomes 2 days, 32-33º C recovery to moderate disability • No difference in 52.2% vs 36.4% (not significant) complications (except • Significantly fewer seizures in seizures) hypothermia group

44 Prophylactic Hypothermia Evidence Supporting Recommendations (continued) STUDY RESULTS CONCLUSION

Hypothermia vs Normothermia

Clifton, 2001 • Mortality: 28% vs 27%; p=.79 • No significant difference RCT; Class 2; n=392 • GOS 6 months poor outcomes • Trend toward poor 2 days, 33º C • 57% vs 57% outcomes hypothermic on arrival, randomized to normothermia. Jiang, 2000 • Mortality: 25.6% vs 45.5% • Better outcomes with RCT; Class 2; n=87 • GOS at 1 year: good recovery to hypothermia Long (3-14 days) mild moderate disability 46.5% vs hypothermia 27.3%; p<.05 • No significant difference in complications

45 Prophylactic Hypothermia Evidence Supporting Recommendations (continued) STUDY RESULTS CONCLUSION

Hypothermia vs Normothermia

Marion, 1997 • GOS at 3 mos good recovery • In subgroup analysis RCT; Class 2; n=82 38% vs 17% p=.03 patients with initial GCS 2 days, 32-33º C • GOS 1 year 62% vs 38% p = of 3 or 4 did not benefit, .05 those with GCS 5 to 7 did benefit from hypothermia

Qiu, 2005 • Mortality: 25.6% vs 51.2%; • Better outcomes RCT; Class 2; n=86 p<.05 • More complications mild hypothermia • GOS 2 years good recovery to (33-35º C) for 3-5 days moderate disability 65.1% vs 37.2%; p<.05 • More pulmonary infections and thrombocytopenia in hypothermia group

46 Nutrition Evidence Overview

10 new studies; 13 from prior edition • Six Class 2 support recommendations • Four Class 2 studies address additional topics but provide insufficient evidence for recommendations • Thirteen Class 3 included as lower level of evidence Study Number Quality of Topic of Studies Evidence OVERALL QUALITY – Class 1 and 2 Timing of feeding 3 RCTs Moderate 2 Retrospective Cohorts Method of feeding 1 RCT Low

Glycemic control 3 RCTs Insufficient

Vitamins and supplements 1 RCT Insufficient

47 Nutrition

EvidenceSTUDY SupportingRESULTS Recommendations CONCLUSION

Timing of Feeding

Chourdakis, 2012* • Outcomes: Pneumonia (VAP and • No difference in RCT; Class 2; n=59 non VAP), CNS infections , outcomes Early(24-48 hours) vs hyperglycemia, bacteremia, UTIs, • Early group more delayed (>48 hours) feeding intolerance: All no kcal/day at all time significant difference points and different hormonal changes Hartl, 2008* • Mortality 2 weeks • Nutritional support Cohort; Class 2; n=797 • Not fed by day 7 within 5 days was Later vs Feed within 5 OR 4.10; p=.0008 associated with a or 7 day • Never max nutrition by significant reduction in day 7 2-week mortality. OR 1.41; p=.004 • Not fed by day 6 OR 2.05; p=.04 • Never max nutrition by day 5 OR 1.30; p=.03

48 Nutrition Evidence Supporting Recommendations (continued) STUDY RESULTS CONCLUSION

Timing of Feeding

Lepellietier, 2010* • Early ventilator associated • Findings suggest early Cohort; Class 2; n=161 pneumonia (EVAP) with early feeding was protective, Impact of early enteral feeding resulting in lower rates feeding (24 hours after OR 0.33; p=.022 of EVAP trauma) Rapp, 1983 • Mortality: 0/20 vs 8/18; p<.001 • Early feeding reduced RCT; Class 2; n=38 mortality from TBI Total parenteral nutrition vs standard enteral nutrition Taylor, 1999 • GOS: trend toward improvement at • No sustained RCT; Class 2; n=82 3 months, no difference at 6 months difference in outcomes Early enhanced feeding • Fewer infections in early feeding vs standard group

49 Nutrition Evidence Supporting Recommendations (continued) STUDY RESULTS CONCLUSION

Method of Feeding

Acosta-Escribano, • All pneumonia OR 0.3; p=.01 • TPF results in less 2010* • Early pneumonia no difference pneumonia than GF RCT; Class 2; n=104 • Late pneumonia OR 0.2; p=.02 feeding; primarily due to transpyloric feeding differences in late (TPF) vs. gastric pneumonia feeding (GF) route

50 Ventilation Therapies Evidence Overview

No new studies; 1 from prior edition • One Class 2 supports recommendation

Study Number Quality of Topic of Studies Evidence OVERALL QUALITY – Class 1 and 2 Influence of hyperventilation on outcomes 1 RCT Low

51 Ventilation Therapies Evidence Supporting Recommendations STUDY RESULTS CONCLUSION Influence of hyperventilation on outcomes

Muizelaar, 1991 GOS HV vs. control • Hyperventilation is RCT; Class 2; n=113 • 3 months HV worse, p<0.03. associated with worse Prolonged • 6 months HV worse, p<0.05. outcomes hyperventilation (HV) vs • 12 months – Not statistically normal ventilation significant.

• Difference is due to patients with Motor score 4-5; no difference in patients with score 1-3.

52 Blood Pressure Thresholds Evidence Overview

3 new studies; One Class 2 supports the recommendation • Two new Class 3-lower level of evidence

Study Number Quality of Topic of Studies Evidence OVERALL QUALITY – Class 2 Hypotension Threshold 1 Cohort Low

53 Blood Pressure Thresholds Evidence Supporting Recommendations STUDY RESULTS CONCLUSION Influence of hyperventilation on outcomes

Berry, 2012* Optimal threshold of hypotension (to • Results suggest the Cohort; Class 2; minimize probability of death) threshold for n=15,733 hypotension in (26.9% GCS ≤8) • 110 mm Hg for patients 15–49 moderate to severe TBI years (AOR 1.98, 95% CI 1.65 to patients should be 110 To determine if a higher 2.39), p<0.0001. or 100 mm Hg systolic hypotension threshold is • 100 mm Hg for patients 50–69 blood pressure. needed for patients with years (AOR 2.20, 95% CI 1.46 to moderate to severe TBI. 3.31), p=0.0002. • 110 mm Hg for patients70 years and older (AOR 1.92, 95% CI 1.35 to 2.74),p=0.0003.

54 Intracranial Pressure Thresholds Evidence Overview

3 new studies; 9 from prior edition • One Class 2 and two Class 3 studies informed the recommendations

Study Number Quality of Topic of Studies Evidence

OVERALL QUALITY – Class 2 ICP Threshold 1 Cohort Low

OVERALL QUALITY – Class 3

Factors other than ICP to consider 3 Cohorts Low

55 Intracranial Pressure Thresholds Evidence Supporting Recommendations STUDY RESULTS CONCLUSION

ICP Thresholds

Sorrentino, 2012* • Mortality: 22 mm Hg for reduced • 22 mm Hg is the Cohort; Class 2; n=459 mortality threshold for reduced • Favorable outcomes: 18 mm Hg mortality Identification of ICP and for favorable outcomes in women CPP thresholds and older patients

56 Intracranial Pressure Thresholds Evidence Supporting Recommendations (continued) STUDY RESULTS CONCLUSION

Factors to consider

Andrews, 1988 • Signs of herniation were • Location of mass lesion Cohort; Class 3; n=45 significantly more common with should be considered in temporal or temporoparietal guiding treatment Effect of hematoma lesions. location on outcome • Clot size of 30 cc was the threshold value for increased incidence of herniation. Chambers, 2001 • ICP threshold for all patients was • It may be inappropriate Series; Class 3; n=207 35 mm Hg to set a single target • Threshold ranged from 22 – 36 for ICP, as higher values Effect of CT different CT classifications may be tolerated in classification certain CT classifications Marshall, 1979 • Patients managed with ICP • Lower threshold may Cohort; Class 3; n=100 monitoring and a threshold of 15 improve outcomes mm HG had improved outcomes (comparison to published reports)

57 Cerebral Perfusion Pressure Thresholds Evidence Overview

9 new studies; 7 from prior edition • Two Class 2 and one Class 3 studies informed the recommendations

Study Number Quality of Topic of Studies Evidence

OVERALL QUALITY – Class 2 and 3 CPP Target 1 RCT Low 2 Cohorts OVERALL QUALITY – Class 3

Negative impact of increasing CPP with 1 RCT reanalysis Low pressors and fluids

58 Cerebral Perfusion Pressure Thresholds Evidence Supporting Recommendations STUDY RESULTS CONCLUSION

CPP Target

Allen, 2014* Survivors/Non-survivors # (%) • Survival is better for Cohort; Class 2; n=1757 • CPP high (>60) adults with high CPP vs. Identification of CPP 701(84.0%)/134 (16.1%) adults with low CPP thresholds • CPP 50-60 562 (83.6%)/110 (16.4%) • CPP low (<50) 147 (62.3%)/89 (37.7%). • RR: low to high 2.35; p<0.0001 Sorrentino, 2012* • Mortality: 70 mm Hg for reduced • 70 mm Hg is the Cohort; Class 2; n=459 mortality threshold for reduced • Favorable outcomes: 70 mm Hg mortality and favorable Identification of ICP and for favorable outcomes outcomes CPP thresholds

59 Cerebral Perfusion Pressure Thresholds Evidence Supporting Recommendations (continued) STUDY RESULTS CONCLUSION

CPP Target

Robertson, 1999 • Neurologic outcomes: no difference • Management that RCT; Class 3; n=189 • Higher CPP had few jugular increases CPP can Comparison of protocol desaturations. result in respiratory with CPP over 70 mm • Adult respiratory distress syndrome distress Hg to protocol with CPP was 5 times greater in the CBF- over 50 mm Hg targeted group, p=0.007.

Contant, 2001 • 5 fold increase in risk of ARDS in • Use of pressors to Series; Class 3; n=189 CPP group strongly related to use increase CPP can have Factors related to the of pressors negative affects. occurrence of ARDS

60 Deep Vein Thrombosis Prophylaxis Evidence Overview

6 New Indirect Studies; 1 from prior edition • Four Class 3 studies provide indirect evidence (mixed severities) • Three Class 3 indirect studies address additional topics but provide insufficient evidence for recommendations Study Number Quality of Topic of Studies Evidence OVERALL QUALITY – Class 3 DVT prophylaxis 4 Retrospective cohorts Low Prophylaxis protocol 2 Pre/Post Insufficient Early vs. late prophylaxis 1 Retrospective cohort Insufficient adminis-tration18

61 Deep Vein Thrombosis Prophylaxis Evidence Supporting Recommendations STUDY RESULTS CONCLUSION

DVT prophylaxis vs none

Daley, 2015* • Mortality: higher rate for no • Prophylaxis is Cohort; Class 3; n=271 treatment group associated with lower • Rates of venous mortality Enoxaparin for thromboembolism, mechanical craniotomy patients ventilation day, hospital length of stay: no significant difference Kwaitt, 2012* • Progression of bleed: 42% (93) vs. • Given higher risk of Cohort; Class 3; n=1215 24% (239), p<0.0001 hemorrhage, risk may • Neurosurgical intervention for exceed benefit Low molecular weight bleed: 14.5% (32) vs. 4.9% (49), heparin for prophylaxis p<0.001 vs none • VTE: 9.1% (20) vs. 3.1% (31), p<0.001

62 Deep Vein Thrombosis Prophylaxis Evidence Supporting Recommendations (continued) STUDY RESULTS CONCLUSION

DVT prophylaxis vs none

Mohseni, 2012* • Mortality: 5% vs 19%; p=.001 • Reduced risk of VTE Case control; Class 3; • VTE: 11% vs 30%; OR of VTE in n=78 control 3.5; p.002 • ICU: no significant difference Anticoagulants vs none • No adverse outcomes or complications Scudday, 2011* Prophylaxis vs. None • Reduced VTE and no Cohort; Class 3; n=812 • VTE :1% (3) vs. 3% (11); p=0.019. significant increase in • Injury progression: 6% (25) vs. 3% bleeding Prophylaxis vs none (11) vs. p=0.055.