Neurocritical Care Approaches to Intracerebral Hemorrhage

Educational Objectives

The goal of this program is to improve treatment of patients with intracerebral hemorrhage. After hearing and assimilating this program, the clinician will be better able to:

1. Weigh the advantages and disadvantages of thrombolytic therapy in patients with intraventricular hemorrhage.
2. Implement strategies to manage infectious and noninfectious fever in critically ill neurologic patients.

Summary

Intraventricular hemorrhage (IVH): independent predictor of poor clinical outcome; if all ventricles affected, mortality rate 90%; leads to refractory intracranial hypertension; many patients require ventriculoperitoneal shunts

Complications: IVH can lead to hydrocephalus, ventricular enlargement, and other complications; delayed communicating hydrocephalus — hydrocephalus develops days to weeks after evacuation of IVH and removal of external ventricular drain (EVD) because of residual protein; elevated intracranial pressure (ICP) — leads to reduced cerebral perfusion pressure; local ischemia — can affect periventricular area; edema — tissues around ventricles swell; delayed cerebral ischemia — stroke occurs later on

Thrombolytic therapy: tissue plasminogen activator (tPA) generally safe in patients with IVH; ventriculitis can develop, but rates similar to those found with placebo; bleeding most prevalent adverse event (typically around ventriculostomy catheter); risk of bleeding reduced with lower dose of tPA (similar to rate for placebo); elevated ICP can develop when EVD closed after administration of tPA; treatment recommended when ICP >25 mm Hg; elevated ICP results in decreased cerebral perfusion pressure

Placement of EVD: study found ICP levels higher in patients with EVD in ipsilateral ventricle than in those with contralateral ventriculostomy; in practice, EVD generally placed in contralateral ventricles to prevent clotting; bilateral EVD not required in all cases, but clinicians should recognize compartmentalization of ICP; majority of deaths associated with ICP >30 mm Hg

CLEAR III trial: found benefit of tPA increased with increasing size of IVH (benefit greatest with IVH >20 mL); tPA may play role in treating IVH <20 mL, but only limited benefit found; results not influenced by age, sex, or Glasgow Coma Scale score on admission; inclusion criteria — stable IVH, absence of bleeding around ventriculostomy, and absence of vascular malformation; timing — participants enrolled <72 hr from onset; good outcomes more likely in those treated <48 hr after ictus; starting tPA as soon as IVH stable potentially beneficial; results — use of tPA did not substantially improve functional outcomes compared with placebo, but did reduce rate of mortality significantly (10%); majority of positive outcomes reported in patients with IVH >20 mL; standard of care cannot change based only on subgroup analysis

Fever: independent predictor of death in critically ill patients; rate of central fever (CF) in neurointensive care unit ≈33%

Significant predictors: study — found fever associated with IVH, volume of intracerebral hemorrhage (ICH) ≈40 mL, ventriculostomy, high white blood cell count, positive microbial cultures, endotracheal tube, central line, longer length of stay, and higher rate of in-hospital mortality; infectious fever associated with greater length of stay; noninfectious fever associated with higher rate of in-hospital mortality; fever found in >33% of patients with ICH; systemic inflammatory response syndrome (SIRS) — study including 10-yr data of patients with ICH found temperature >38.3°C in ≈20% on first day; in ≈25% on second day; 90% of patients met ≥2 SIRS criteria (prevalence in neurointensive care unit high); however, authors found only 1 positive result in 432 blood cultures; factors associated with starting antibiotic drugs — young age, male sex, fever, SIRS, and false-positive cultures

Infectious and noninfectious fever: factors associated with CF — young age, subarachnoid hemorrhage (SAH), IVH, brain tumor, blood transfusion in neurointensive care unit, onset of fever within 72 hr of admission, and persistent fever (fluctuating or intermittent fever typically infectious or drug-induced); factors associated with infectious fever — status epilepticus, central venous catheter, long duration of mechanical ventilation, infiltrate revealed by chest radiography, and longer length of stay in intensive care unit; exclusion criteria — negative blood cultures, absence of infiltrate on chest radiography, SAH, IVH, tumor, and onset of fever within 72 hr indicate probability of CF 90%; if fever noninfectious, discontinue antibiotic drugs within 72 hr; continuing antibiotic therapy beyond 72 hr in patients without infection increases risk for morbidity and mortality

Treatment: study found combination of acetaminophen (Tylenol) and ibuprofen more effective for control of fever than acetaminophen or ibuprofen alone; ibuprofen monotherapy superior to acetaminophen monotherapy; in patients with fever after ventriculostomy, ibuprofen and acetaminophen may be alternated every 3 hr; ibuprofen not associated with complications in patients with ICH

Treatment of perihematomal edema: in patients treated within 72 hr with hypertonic saline infusion (administered to achieve sodium 145-155 mmol/L), volume of perihematomal edema lower compared with patients treated with regular saline solution; perihematomal edema associated with poor outcome; however, excess sodium can trigger hyperchloremic metabolic acidosis

Administration of fluids: large study compared balanced crystalloids (lactated Ringer’s solution) with saline solution; found use of balanced crystalloids resulted in better outcomes in critically ill neurologic patients; effects not clear in patients with traumatic brain injury; reducing sodium concentration (to, eg, 140 mmol/L) may prevent adverse events associated with hypertonic saline solution

Therapeutic hypothermia: multiple mechanisms involved in reduction of edema using hypothermia; study compared therapeutic hypothermia with conventional management of temperature for 8 to 10 days in patients with ICH; in therapeutic hypothermia arm, target temperature 35.0°C achieved, followed by slow rewarming to avoid rebound increases in ICP; patients who underwent hypothermia found to have longer length of stay; mild hypothermia prevented infectious complications (eg, pneumonia); at 3 mo, modified Rankin scale (mRS) scores better in hypothermia arm than control arm; scores improved overall at 1 yr, but no patients in control arm achieved mRS score <3; rate of mortality in patients in hypothermia arm lower; applicability of results limited by small size of sample; clinicians can consider therapeutic hypothermia as adjunct to hypertonic saline therapy or evacuation

Readings

Gillow SJ et al: Factors associated with fever in intracerebral hemorrhage. J Stroke Cerebrovasc Dis. 2017 Jun;26(6):1204-8; Hanley DF et al: Thrombolytic removal of intraventricular haemorrhage in treatment of severe stroke: results of the randomised, multicentre, multiregion, placebo-controlled CLEAR III trial. Lancet. 2017 Feb 11;389(10069):603-11; Kollmar R et al: Cooling in intracerebral hemorrhage (CINCH) trial: protocol of a randomized German-Austrian clinical trial. Int J Stroke. 2012 Feb;7(2):168-72; Mullins ME et al: A prospective randomized study to evaluate the antipyretic effect of the combination of acetaminophen and ibuprofen in neurological ICU patients. Neurocrit Care. 2011 Dec;15(3):375-8; Naff N et al: Low-dose recombinant tissue-type plasminogen activator enhances clot resolution in brain hemorrhage: the intraventricular hemorrhage thrombolysis trial. Stroke. 2011 Nov;42(11):3009-16; Semler MW et al: Balanced crystalloids versus saline in critically ill adults. N Engl J Med. 2018 Mar 1;378(9):829-39; Wagner I et al: Effects of continuous hypertonic saline infusion on perihemorrhagic edema evolution. Stroke. 2011 Jun;42(6):1540-5; Webb AJ et al: Resolution of intraventricular hemorrhage varies by ventricular region and dose of intraventricular thrombolytic: the Clot Lysis: Evaluating Accelerated Resolution of IVH (CLEAR IVH) program. Stroke. 2012 Jun;43(6):1666-8.

Disclosures

For this program, members of the faculty and planning committee reported nothing to disclose.

Acknowledgements

Dr. Emanuel was recorded at the 2019 Annual Cerebrovascular Disease Symposium: From Clinical Trial to Clinical Practice, presented by the Keck School of Medicine, University of Southern California, and held October 5, 2019, in Los Angeles, CA. For information about upcoming CME conferences presented by the Keck School of Medicine, University of Southern California, please visit Keck.usc.edu. The Audio Digest Foundation thanks the speakers and sponsors for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

NE110301

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.