Mary Presciutti

Impact of tight glycemic control on cerebral glucose metabolism after severe brain injury: A microdialysis study*

Objectives:To analyze the effect of tight glycemic control with the use of intensive insulin therapy on cerebral glucose metabolism in patients with severe brain injury. Design:Retrospective analysis of a prospective observational cohort. Setting:University hospital neurologic intensive care unit. Patients:Twenty patients (median age 59 yrs) monitored with cerebral microdialysis as part of their clinical care. Interventions:Intensive insulin therapy (systemic glucose target: 4.4–6.7 mmol/L [80–120 mg/dL]). Measurements and Main Results:Brain tissue markers of glucose metabolism (cerebral microdialysis glucose and lactate/pyruvate ratio) and systemic glucose were collected hourly. Systemic glucose levels were categorized as within the target “tight” (4.4–6.7 mmol/L [80–120 mg/dL]) vs. “intermediate” (6.8–10.0 mmol/L [121–180 mg/dL]) range. Brain energy crisis was defined as a cerebral microdialysis glucose <0.7 mmol/L with a lactate/pyruvate ratio >40. We analyzed 2131 cerebral microdialysis samples: tight systemic glucose levels were associated with a greater prevalence of low cerebral microdialysis glucose (65% vs. 36%, p < 0.01) and brain energy crisis (25% vs.17%, p < 0.01) than intermediate levels. Using multivariable analysis, and adjusting for intracranial pressure and cerebral perfusion pressure, systemic glucose concentration (adjusted odds ratio 1.23, 95% confidence interval [CI] 1.10–1.37, for each 1 mmol/L decrease, p < 0.001) and insulin dose (adjusted odds ratio 1.10, 95% CI 1.04–1.17, for each 1 U/hr increase, p = 0.02) independently predicted brain energy crisis. Cerebral microdialysis glucose was lower in nonsurvivors than in survivors (0.46 ± 0.23 vs. 1.04 ± 0.56 mmol/L, p < 0.05). Brain energy crisis was associated with increased mortality at hospital discharge (adjusted odds ratio 7.36, 95% CI 1.37–39.51, p = 0.02). Conclusions:In patients with severe brain injury, tight systemic glucose control is associated with reduced cerebral extracellular glucose availability and increased prevalence of brain energy crisis, which in turn correlates with increased mortality. Intensive insulin therapy may impair cerebral glucose metabolism after severe brain injury.

Clinical trial of a novel surface cooling system for fever control in neurocritical care patients

Objective:To compare the efficacy of a novel water-circulating surface cooling system with conventional measures for treating fever in neuro-intensive care unit patients. Design:Prospective, unblinded, randomized controlled trial. Setting:Neurologic intensive care unit in an urban teaching hospital. Patients:Forty-seven patients, the majority of whom were mechanically ventilated and sedated, with fever ≥38.3°C for >2 consecutive hours after receiving 650 mg of acetaminophen. Interventions:Subjects were randomly assigned to 24 hrs of treatment with a conventional water-circulating cooling blanket placed over the patient (Cincinnati SubZero, Cincinnati OH) or the Arctic Sun Temperature Management System (Medivance, Louisville CO), which employs hydrogel-coated water-circulating energy transfer pads applied directly to the trunk and thighs. Measurements and Main Results:Diagnoses included subarachnoid hemorrhage (60%), cerebral infarction (23%), intracerebral hemorrhage (11%), and traumatic brain injury (4%). The groups were matched in terms of baseline variables, although mean temperature was slightly higher at baseline in the Arctic Sun group (38.8 vs. 38.3°C, p = .046). Compared with patients treated with the SubZero blanket (n = 24), Arctic Sun-treated patients (n = 23) experienced a 75% reduction in fever burden (median 4.1 vs. 16.1 C°-hrs, p = .001). Arctic Sun-treated patients also spent less percent time febrile (T ≥38.3°C, 8% vs. 42%, p < .001), spent more percent time normothermic (T ≤37.2°C, 59% vs. 3%, p < .001), and attained normothermia faster than the SubZero group median (2.4 vs. 8.9 hrs, p = .008). Shivering occurred more frequently in the Arctic Sun group (39% vs. 8%, p = .013). Conclusion:The Arctic Sun Temperature Management System is superior to conventional cooling-blanket therapy for controlling fever in critically ill neurologic patients.

Cerebral Perfusion Pressure Thresholds for Brain Tissue Hypoxia and Metabolic Crisis After Poor-Grade Subarachnoid Hemorrhage

Background and Purpose— To identify a minimally acceptable cerebral perfusion pressure threshold above which the risks of brain tissue hypoxia (BTH) and oxidative metabolic crisis are reduced for patients with subarachnoid hemorrhage (SAH). Methods— We studied 30 poor-grade SAH patients who underwent brain multimodality monitoring (3042 hours). Physiological measures were averaged over 60 minutes for each collected microdialysis sample. Metabolic crisis was defined as a lactate/pyruvate ratio >40 with a brain glucose concentration ⩽0.7 mmol/L. BTH was defined as PbtO2 <20 mm Hg. Outcome was assessed at 3 months with the Modified Rankin Scale. Results— Multivariable analyses adjusting for admission Hunt-Hess grade, intraventricular hemorrhage, systemic glucose, and end-tidal CO2 revealed that cerebral perfusion pressure ⩽70 mm Hg was significantly associated with an increased risk of BTH (OR, 2.0; 95% CI, 1.2–3.3; P=0.007) and metabolic crisis (OR, 2.1; 95% CI, 1.2–3.7; P=0.007). Death or severe disability at 3 months was significantly associated with metabolic crisis (OR, 5.4; 95% CI, 1.8–16; P=0.002) and BTH (OR, 5.1; 95% CI, 1.2–23; P=0.03) after adjusting for admission Hunt-Hess grade. Conclusions— Metabolic crisis and BTH are associated with mortality and poor functional recovery after SAH. Cerebral perfusion pressure levels <70 mm Hg was associated with metabolic crisis and BTH, and may increase the risk of secondary brain injury in poor-grade SAH patients.

Prevention of Shivering During Therapeutic Temperature Modulation: The Columbia Anti-Shivering Protocol

BackgroundAs the practice of aggressive temperature control has become more commonplace, new clinical problems are arising, of which shivering is the most common. Treatment for shivering while avoiding the negative consequences of many anti-shivering therapies is often difficult. We have developed a stepwise protocol that emphasizes use of the least sedating regimen to achieve adequate shiver control.MethodsAll patients treated with temperature modulating devices in the neurological intensive care unit were prospectively entered into a database. Baseline demographic information, daily temperature goals, best daily GCS, and type and cumulative dose of anti-shivering agents were recorded.ResultsWe collected 213 patients who underwent 1388 patient days of temperature modulation. Eighty-nine patients underwent hypothermia and 124 patients underwent induced normothermia. In 18% of patients and 33% of the total patient days only none-sedating baseline interventions were needed. The first agent used was most commonly dexmeditomidine at 50% of the time, followed by an opiate and increased doses of propofol. Younger patients, men, and decreased BSA were factors associated with increased number of anti-shivering interventions.ConclusionsA significant proportion of patients undergoing temperature modulation can be effectively treated for shivering without over-sedation and paralysis. Patients at higher risk for needing more interventions are younger men with decreased BSA.

Status Epilepticus–Induced Hyperemia and Brain Tissue Hypoxia After Cardiac Arrest

OBJECTIVE To report changes of cerebral blood flow and metabolism associated with status epilepticus after cardiac arrest. DESIGN Case report. SETTING Neurological intensive care unit in a university hospital. PATIENT An 85-year-old man resuscitated from out-of-hospital cardiac arrest underwent brain multimodality monitoring and treatment with therapeutic hypothermia. MAIN OUTCOME MEASURES Changes of cerebral blood flow and metabolism. RESULTS Repetitive electrographic seizure activity detected at the start of monitoring was associated with dramatic reductions in brain tissue oxygen tension and striking surges in cerebral blood flow and brain temperature. Intravenous lorazepam and levetiracetam administration resulted in immediate cessation of the seizures and these associated derangements. The lactate to pyruvate ratio was initially elevated and trended down after administration of anticonvulsants. CONCLUSION Brain multimodality monitoring is a feasible method for evaluating secondary brain injury associated with seizure activity after cardiac arrest.

Effect of mannitol on brain metabolism and tissue oxygenation in severe haemorrhagic stroke

Background The impact of osmotic therapies on brain metabolism has not been extensively studied in humans. The authors examined if mannitol treatment of raised intracranial pressure will result in an improvement in brain metabolism together with the expected drop in intracranial pressure (ICP). Methods This is a retrospective review of prospectively collected data. Twenty episodes of raised ICP (>20 mm Hg) resistant to standard therapy that required infusions of mannitol were studied in 12 comatose patients with multimodality monitoring including ICP, PbtO2 and microdialysis. The authors compared mean arterial blood pressure, ICP, cerebral perfusion pressure, PbtO2, brain lactate, pyruvate and glucose using cerebral microdialysis, for 3 h preceding and 4 h after hyperosmolar therapy. Time-series data were analysed using a multivariable general linear model utilising generalised estimating equations for model estimation to account for within-subjects and between-subjects variations over time. Results 20% mannitol solution (1 g/kg) was administered at the discretion of the attending neurointensivist. ICP decreased 30 min (from 27±13 to 19±16 mm Hg, p<0.001) and cerebral perfusion pressure increased 45 min (from 73± 18 to 85±22 mm Hg, p=0.002) after the start of mannitol infusions, whereas mean arterial blood pressure and PbtO2 did not change significantly. The peak lactate–pyruvate ratio was recorded at the time of initiating osmotherapy (44±20) with an 18% decrease over 2 h following mannitol therapy (35±16; p=0.002). Brain glucose remained unaffected. Conclusions Mannitol effectively reduces ICP and appeared to benefit brain metabolism as measured by the lactate–pyruvate ratio.

Nutritional support and brain tissue glucose metabolism in poor-grade SAH: a retrospective observational study

IntroductionWe sought to determine the effect of nutritional support and insulin infusion therapy on serum and brain glucose levels and cerebral metabolic crisis after aneurysmal subarachnoid hemorrhage (SAH).MethodsWe used a retrospective observational cohort study of 50 mechanically ventilated poor-grade (Hunt-Hess 4 or 5) aneurysmal SAH patients who underwent brain microdialysis monitoring for an average of 109 hours. Enteral nutrition was started within 72 hours of admission whenever feasible. Intensive insulin therapy was used to maintain serum glucose levels between 5.5 and 7.8 mmol/l. Serum glucose, insulin and caloric intake from enteral tube feeds, dextrose and propofol were recorded hourly. Cerebral metabolic distress was defined as a lactate to pyruvate ratio (LPR) > 40. Time-series data were analyzed using a general linear model extended by generalized estimation equations (GEE).ResultsDaily mean caloric intake received was 13.8 ± 6.9 cal/kg and mean serum glucose was 7.9 ± 1 mmol/l. A total of 32% of hourly recordings indicated a state of metabolic distress and < 1% indicated a state of critical brain hypoglycemia (< 0.2 mmol/l). Calories received from enteral tube feeds were associated with higher serum glucose concentrations (Wald = 6.07, P = 0.048), more insulin administered (Wald = 108, P < 0.001), higher body mass index (Wald = 213.47, P < 0.001), and lower body temperature (Wald = 4.1, P = 0.043). Enteral feeding (Wald = 1.743, P = 0.418) was not related to brain glucose concentrations after accounting for serum glucose concentrations (Wald = 67.41, P < 0.001). In the presence of metabolic distress, increased insulin administration was associated with a relative reduction of interstitial brain glucose concentrations (Wald = 8.26, P = 0.017), independent of serum glucose levels.ConclusionsIn the presence of metabolic distress, insulin administration is associated with reductions in brain glucose concentration that are independent of serum glucose levels. Further study is needed to understand how nutritional support and insulin administration can be optimized to minimize secondary injury after subarachnoid hemorrhage.