Suzanne Frangos

Packed red blood cell transfusion increases local cerebral oxygenation.

Objective:To determine a) whether packed red blood cell transfusion (RBCT) increases local brain tissue oxygen partial pressure (Pbto2) in a neurocritical care population; and b) what (if any) demographic, clinical, or physiologic variables mediate the assumed change. Design:Prospective observational study. Setting:A neurosurgical intensive care unit at a university-based level I trauma center and tertiary care hospital. Patients:Thirty-five consecutive volume-resuscitated patients with subarachnoid hemorrhage or traumatic brain injury, without cardiac disease, requiring Pbto2 monitoring and receiving RBCT were studied between October 2001 and December 2003. Interventions:None. Measurements and Main Results:The following physiologic variables were measured and compared 1 hr before and after RBCT: Pbto2, intracranial pressure, cerebral perfusion pressure, hemoglobin oxygen saturation (Sao2), Fio2, hemoglobin, and hematocrit. An increase in Pbto2 was observed in 26 of the 35 patients (74%). In nine patients, Pbto2 decreased after RBCT. The mean (±sd) increase in Pbto2 for all patients was 3.2 ± 8.8 mm Hg (p = .02), a 15% change from baseline (1 hr before RCBT). This Pbto2 increase was associated with a significant mean increase in hemoglobin and hematocrit after RBCT (1.4 ± 1.1 g/dL and 4.2% ± 3.3%, respectively; both p < .001). Cerebral perfusion pressure, Sao2, and Fio2 were similar before and after RBCT. Among the 26 patients whose Pbto2 increased, the mean increase in Pbto2 was 5.1 ± 9.4 mm Hg or a 49% mean increase (p < .01). Conclusions:RBCT is associated with an increase in Pbto2 in most patients with subarachnoid hemorrhage or traumatic brain injury. This mean increase appears to be independent of cerebral perfusion pressure, Sao2, and Fio2. Further study is required to determine why Pbto2 decreases in some patients after RBCT.

Effect of mannitol and hypertonic saline on cerebral oxygenation in patients with severe traumatic brain injury and refractory intracranial hypertension

Background: The impact of osmotic therapies on brain oxygen has not been extensively studied in humans. We examined the effects on brain tissue oxygen tension (PbtO2) of mannitol and hypertonic saline (HTS) in patients with severe traumatic brain injury (TBI) and refractory intracranial hypertension. Methods: 12 consecutive patients with severe TBI who underwent intracranial pressure (ICP) and PbtO2 monitoring were studied. Patients were treated with mannitol (25%, 0.75 g/kg) for episodes of elevated ICP (>20 mm Hg) or HTS (7.5%, 250 ml) if ICP was not controlled with mannitol. PbtO2, ICP, mean arterial pressure, cerebral perfusion pressure (CPP), central venous pressure and cardiac output were monitored continuously. Results: 42 episodes of intracranial hypertension, treated with mannitol (n = 28 boluses) or HTS (n = 14 boluses), were analysed. HTS treatment was associated with an increase in PbtO2 (from baseline 28.3 (13.8) mm Hg to 34.9 (18.2) mm Hg at 30 min, 37.0 (17.6) mm Hg at 60 min and 41.4 (17.7) mm Hg at 120 min; all p<0.01) while mannitol did not affect PbtO2 (baseline 30.4 (11.4) vs 28.7 (13.5) vs 28.4 (10.6) vs 27.5 (9.9) mm Hg; all p>0.1). Compared with mannitol, HTS was associated with lower ICP and higher CPP and cardiac output. Conclusions: In patients with severe TBI and elevated ICP refractory to previous mannitol treatment, 7.5% hypertonic saline administered as second tier therapy is associated with a significant increase in brain oxygenation, and improved cerebral and systemic haemodynamics.

Brain Lactate Metabolism in Humans With Subarachnoid Hemorrhage

Background and Purpose— Lactate is central for the regulation of brain metabolism and is an alternative substrate to glucose after injury. Brain lactate metabolism in patients with subarachnoid hemorrhage has not been fully elucidated. Methods— Thirty-one subarachnoid hemorrhage patients monitored with cerebral microdialysis (CMD) and brain oxygen (PbtO2) were studied. Samples with elevated CMD lactate (>4 mmol/L) were matched to PbtO2 and CMD pyruvate and categorized as hypoxic (PbtO2 <20 mm Hg) versus nonhypoxic and hyperglycolytic (CMD pyruvate >119 &mgr;mol/L) versus nonhyperglycolytic. Results— Median per patient samples with elevated CMD lactate was 54% (interquartile range, 11%–80%). Lactate elevations were more often attributable to cerebral hyperglycolysis (78%; interquartile range, 5%–98%) than brain hypoxia (11%; interquartile range, 4%–75%). Mortality was associated with increased percentage of samples with elevated lactate and brain hypoxia (28% [interquartile range 9%–95%] in nonsurvivors versus 9% [interquartile range 3%–17%] in survivors; P=0.02) and lower percentage of elevated lactate and cerebral hyperglycolysis (13% [interquartile range, 1%–87%] versus 88% [interquartile range, 27%–99%]; P=0.07). Cerebral hyperglycolytic lactate production predicted good 6-month outcome (odds ratio for modified Rankin Scale score, 0–3 1.49; CI, 1.08–2.05; P=0.016), whereas increased lactate with brain hypoxia was associated with a reduced likelihood of good outcome (OR, 0.78; CI, 0.59–1.03; P=0.08). Conclusions— Brain lactate is frequently elevated in subarachnoid hemorrhage patients, predominantly because of hyperglycolysis rather than hypoxia. A pattern of increased cerebral hyperglycolytic lactate was associated with good long-term recovery. Our data suggest that lactate may be used as an aerobic substrate by the injured human brain.

Brain hypoxia is associated with short-term outcome after severe traumatic brain injury independently of intracranial hypertension and low cerebral perfusion pressure.

BACKGROUND Brain hypoxia (BH) can aggravate outcome after severe traumatic brain injury (TBI). Whether BH or reduced brain oxygen (Pbto2) is an independent outcome predictor or a marker of disease severity is not fully elucidated. OBJECTIVE To analyze the relationship between Pbto2, intracranial pressure (ICP), and cerebral perfusion pressure (CPP) and to examine whether BH correlates with worse outcome independently of ICP and CPP. METHODS We studied 103 patients monitored with ICP and Pbto2 for > 24 hours. Durations of BH (Pbto2 < 15 mm Hg), ICP > 20 mm Hg, and CPP < 60 mm Hg were calculated with linear interpolation, and their associations with outcome within 30 days were analyzed. RESULTS Duration of BH was longer in patients with unfavorable (Glasgow Outcome Scale score, 1-3) than in those with favorable (Glasgow Outcome Scale, 4-5) outcome (8.3 ± 15.9 vs 1.7 ± 3.7 hours; P < .01). In patients with intracranial hypertension, those with BH had fewer favorable outcomes (46%) than those without (81%; P < .01); similarly, patients with low CPP and BH were less likely to have favorable outcome than those with low CPP but normal Pbto2 (39% vs 83%; P < .01). After ICP, CPP, age, Glasgow Coma Scale score, Marshall computed tomography grade, and Acute Physiology and Chronic Health Evaluation II score were controlled for, BH was independently associated with poor prognosis (adjusted odds ratio for favorable outcome, 0.89 per hour of BH; 95% confidence interval, 0.79-0.99; P = .04). CONCLUSION Brain hypoxia is associated with poor short-term outcome after severe traumatic brain injury independently of elevated ICP, low CPP, and injury severity. Pbto2 may be an important therapeutic target after severe traumatic brain injury. ABBREVIATIONS AOR: adjusted odds ratio APACHE II: Acute Physiology and Chronic Health Evaluation II CI: confidence interval CPP: cerebral perfusion pressure GCS: Glasgow Coma Scale ICP: intracranial pressure IQR: interquartile range MAP: mean arterial pressure TBI: traumatic brain injury

Hemoglobin Concentration and Cerebral Metabolism in Patients With Aneurysmal Subarachnoid Hemorrhage

Background and Purpose— The optimal hemoglobin (Hgb) target after aneurysmal subarachnoid hemorrhage is not precisely known. We sought to examine the threshold of Hgb concentration associated with an increased risk of cerebral metabolic dysfunction in patients with poor-grade subarachnoid hemorrhage. Methods— Twenty consecutive patients with poor-grade subarachnoid hemorrhage who underwent multimodality neuromonitoring (intracranial pressure, brain tissue oxygen tension, cerebral microdialysis) were studied prospectively. Brain tissue oxygen tension and extracellular lactate/pyruvate ratio were used as markers of cerebral metabolic dysfunction and the relationship between Hgb concentrations and the incidence of brain hypoxia (defined by a brain tissue oxygen tension <20 mm Hg) and cell energy dysfunction (defined by a lactate/pyruvate ratio >40) was analyzed. Results— Compared with higher Hgb concentrations, a Hgb concentration <9 g/dL was associated with lower brain tissue oxygen tension (27.2 [interquartile range, 21.2 to 33.1] versus 19.9 [interquartile range, 7.1 to 33.1] mm Hg, P=0.02), higher lactate/pyruvate ratio (29 [interquartile range, 25 to 38] versus 36 [interquartile range, 26 to 59], P=0.16), and an increased incidence of brain hypoxia (21% versus 52%, P<0.01) and cell energy dysfunction (23% versus 43%, P=0.03). On multivariable analysis, a Hgb concentration <9 g/dL was associated with a higher risk of brain hypoxia (OR, 7.92; 95% CI, 2.32 to 27.09; P<0.01) and cell energy dysfunction (OR, 4.24; 95% CI, 1.33 to 13.55; P=0.02) after adjusting for cerebral perfusion pressure, central venous pressure, PaO2/FIO2 ratio, and symptomatic vasospasm. Conclusions— A Hgb concentration <9 g/dL is associated with an increased incidence of brain hypoxia and cell energy dysfunction in patients with poor-grade subarachnoid hemorrhage.

Induced Normothermia Attenuates Cerebral Metabolic Distress in Patients With Aneurysmal Subarachnoid Hemorrhage and Refractory Fever

BACKGROUND AND PURPOSE The purpose of this study was to analyze whether fever control attenuates cerebral metabolic distress after aneurysmal subarachnoid hemorrhage (SAH). METHODS Eighteen SAH patients, who underwent intracranial pressure (ICP) and cerebral microdialysis monitoring and were treated with induced normothermia for refractory fever (body temperature >or=38.3 degrees C, despite antipyretics), were studied. Levels of microdialysate lactate/pyruvate ratio (LPR) and episodes of cerebral metabolic crisis (LPR >40) were analyzed during fever and induced normothermia, at normal and high ICP (>20 mm Hg). RESULTS Compared to fever, induced normothermia resulted in lower LPR (40+/-24 versus 32+/-9, P<0.01) and a reduced incidence of cerebral metabolic crisis (13% versus 5%, P<0.05) at normal ICP. During episodes of high ICP, induced normothermia was associated with a similar reduction of LPR, fewer episodes of cerebral metabolic crisis (37% versus 8%, P<0.01), and lower ICP (32+/-11 versus 28+/-12 mm Hg, P<0.05). CONCLUSIONS Fever control is associated with reduced cerebral metabolic distress in patients with SAH, irrespective of ICP.

Decompressive craniectomy for elevated intracranial pressure and its effect on the cumulative ischemic burden and therapeutic intensity levels after severe traumatic brain injury.

BACKGROUNDIncreased intracranial pressure (ICP) can cause brain ischemia and compromised brain oxygen (PbtO2 ≤ 20 mm Hg) after severe traumatic brain injury (TBI). OBJECTIVEWe examined whether decompressive craniectomy (DC) to treat elevated ICP reduces the cumulative ischemic burden (CIB) of the brain and therapeutic intensity level (TIL). METHODSTen severe TBI patients (mean age, 31.4 ± 14.2 years) who had continuous PbtO2 monitoring before and after delayed DC were retrospectively identified. Patients were managed according to the guidelines for the management of severe TBI. The CIB was measured as the total time spent between a PbtO2 of 15 to 20, 10 to 15, and 0 to 10 mm Hg. The TIL was calculated every 12 hours. Mixed-effects models were used to estimate changes associated with DC. RESULTSDC was performed on average 2.8 days after admission. DC was found to immediately reduce ICP (mean [SEM] decrease was 7.86 mm Hg [2.4 mm Hg]; P = .005). TIL, which was positively correlated with ICP (r = 0.46, P ≤ .001), was reduced within 12 hours after surgery and continued to improve within the postsurgical monitoring period (P ≤ .001). The duration and severity of CIB were significantly reduced as an effect of DC in this group. The overall mortality rate in the group of 10 patients was lower than predicted at the time of admission (P = .015). CONCLUSIONThese results suggest that a DC for increased ICP can reduce the CIB of the brain after severe TBI. We suggest that DC be considered early in a patients clinical course, particularly when the TIL and ICP are increased.

Detection of cerebral compromise with multimodality monitoring in patients with subarachnoid hemorrhage.

BACKGROUND:Studies in traumatic brain injury suggest that monitoring techniques such as brain tissue oxygen (Pbto2) and cerebral microdialysis may complement conventional intracranial pressure (ICP) and cerebral perfusion pressure (CPP) measurements. OBJECTIVE:In this study of poor-grade (Hunt and Hess grade IV and V) subarachnoid hemorrhage (SAH) patients, we examined the prevalence of brain hypoxia and brain energy dysfunction in the presence of normal and abnormal ICP and CPP. METHODS:SAH patients who underwent multimodal neuromonitoring and cerebral microdialysis were studied. We examined the frequency of brain hypoxia and energy dysfunction in different ICP and CPP ranges and the relationship between Pbto2 and the lactate/pyruvate ratio (LPR). RESULTS:A total of 2394 samples from 19 patients were analyzed. There were 149 samples with severe brain hypoxia (Pbto2 ≤10 mm Hg) and 347 samples with brain energy dysfunction (LPR >40). The sensitivities of abnormal ICP or CPP for elevated LPR and reduced Pbto2 were poor (21.2% at best), and the LPR or Pbto2 was abnormal in many instances when ICP or CPP was normal. Severe brain hypoxia was often associated with an LPR greater than 40 (86% of samples). In contrast, mild brain hypoxia (≤20 mm Hg) and severe brain hypoxia were observed in only 53% and 36% of samples with brain energy dysfunction, respectively. CONCLUSION:Our data demonstrate that ICP and CPP monitoring may not always detect episodes of cerebral compromise in SAH patients. Our data suggest that several complementary monitors may be needed to optimize the care of poor-grade SAH patients.

Acute lung injury is an independent risk factor for brain hypoxia after severe traumatic brain injury.

BACKGROUNDPulmonary complications are frequently observed after severe traumatic brain injury (TBI), but little is known about the consequences of lung injury on brain tissue oxygenation and metabolism. OBJECTIVEWe examined the association between lung function and brain tissue oxygen tension (PbtO2) in patients with severe TBI. METHODSWe analyzed data from 78 patients with severe, nonpenetrating TBI who underwent continuous PbtO2 and intracranial pressure monitoring. Acute lung injury was defined by the presence of pulmonary infiltrates with a PaO2/FiO2 (PF) ratio less than 300 and the absence of left ventricular failure. A total of 587 simultaneous measurements of PbtO2 and PF ratio were examined using longitudinal data analysis. RESULTSPbtO2 correlated strongly with PaO2 and PF ratio (P < .05) independent of PaCO2, brain temperature, cerebral perfusion pressure, and hemoglobin. Acute lung injury was associated with lower PbtO2 (34.6 ± 13.8 mm Hg at PF ratio >300 vs 30.2 ± 10.8 mm Hg [PF ratio 200–300], 28.9 ± 9.8 mm Hg [PF ratio 100–199], and 21.1 ± 7.4 mm Hg [PF ratio <100], all P values <.01). After adjusting for intracranial pressure, Marshall computed tomography score, and APACHE II (Acute Physiology and Chronic Health Evaluation) score, acute lung injury was an independent risk factor for compromised PbtO2 (PbtO2 <20 mm Hg; adjusted odds ratio: 2.13, 95% confidence interval: 1.21–3.77; P < .01). CONCLUSIONAfter severe TBI, PbtO2 correlates with PF ratio. Acute lung injury is associated with an increased risk of compromised PbtO2, independent from intracerebral and systemic injuries. Our findings support the use of lung-protective strategies to prevent brain hypoxia in TBI patients.

A Comparison of Clinical and Research Practices in Measuring Cerebral Perfusion Pressure: A Literature Review and Practitioner Survey

BACKGROUND:Our objective was to determine whether there is variability in the foundational literature and across centers in how mean arterial blood pressure is measured to calculate cerebral perfusion pressure. METHODS:We reviewed foundational literature and sent an e-mail survey to members of the Neurocritical Care Society. RESULTS:Of 32 articles reporting cerebral perfusion pressure data, the reference point for mean arterial blood pressure was identified in 16: 10 heart and 6 midbrain. The overall survey response rate was 14.3%. Responses from 31 of 34 (91%) United Council for Neurologic Subspecialties fellowship-accredited Neurointensive Care Units indicated the reference point was most often the heart (74%), followed by the midbrain (16%). Conflicting answers were received from 10%. CONCLUSIONS:There is substantive heterogeneity in both research reports and clinical practice in how mean arterial blood pressure is measured to determine cerebral perfusion pressure.