Systemic glucose variability predicts cerebral metabolic distress and mortality after subarachnoid hemorrhage: a retrospective observational study.

INTRODUCTION: Cerebral glucose metabolism and energy production are affected by serum glucose levels. Systemic glucose variability has been shown to be associated with poor outcome in critically ill patients. The objective of this study was to assess whether glucose variability is associated with cerebral metabolic distress and outcome after subarachnoid hemorrhage. METHODS: A total of 28 consecutive comatose patients with subarachnoid hemorrhage, who underwent cerebral microdialysis and intracranial pressure monitoring, were studied. Metabolic distress was defined as lactate/pyruvate ratio (LPR) >40. The relationship between daily glucose variability, the development of cerebral metabolic distress and hospital outcome was analyzed using a multivariable general linear model with a logistic link function for dichotomized outcomes. RESULTS: Daily serum glucose variability was expressed as the standard deviation (SD) of all serum glucose measurements. General linear models were used to relate this predictor variable to cerebral metabolic distress and mortality at hospital discharge. A total of 3,139 neuromonitoring hours and 181 days were analyzed. After adjustment for Glasgow Coma Scale (GCS) scores and brain glucose, SD was independently associated with higher risk of cerebral metabolic distress (adjusted odds ratio = 1.5 (1.1 to 2.1), P = 0.02). Increased variability was also independently associated with in hospital mortality after adjusting for age, Hunt Hess, daily GCS and symptomatic vasospasm (P = 0.03). CONCLUSIONS: Increased systemic glucose variability is associated with cerebral metabolic distress and increased hospital mortality. Therapeutic approaches that reduce glucose variability may impact on brain metabolism and outcome after subarachnoid hemorrhage.

Reduced brain/serum glucose ratios predict cerebral metabolic distress and mortality after severe brain injury.

BACKGROUND: The brain is dependent on glucose to meet its energy demands. We sought to evaluate the potential importance of impaired glucose transport by assessing the relationship between brain/serum glucose ratios, cerebral metabolic distress, and mortality after severe brain injury. METHODS: We studied 46 consecutive comatose patients with subarachnoid or intracerebral hemorrhage, traumatic brain injury, or cardiac arrest who underwent cerebral microdialysis and intracranial pressure monitoring. Continuous insulin infusion was used to maintain target serum glucose levels of 80-120 mg/dL (4.4-6.7 mmol/L). General linear models of logistic function utilizing generalized estimating equations were used to relate predictors of cerebral metabolic distress (defined as a lactate/pyruvate ratio [LPR] ≥ 40) and mortality. RESULTS: A total of 5,187 neuromonitoring hours over 300 days were analyzed. Mean serum glucose was 133 mg/dL (7.4 mmol/L). The median brain/serum glucose ratio, calculated hourly, was substantially lower (0.12) than the expected normal ratio of 0.40 (brain 2.0 and serum 5.0 mmol/L). In addition to low cerebral perfusion pressure (P = 0.05) and baseline Glasgow Coma Scale score (P < 0.0001), brain/serum glucose ratios below the median of 0.12 were independently associated with an increased risk of metabolic distress (adjusted OR = 1.4 [1.2-1.7], P < 0.001). Low brain/serum glucose ratios were also independently associated with in-hospital mortality (adjusted OR = 6.7 [1.2-38.9], P < 0.03) in addition to Glasgow Coma Scale scores (P = 0.029). CONCLUSIONS: Reduced brain/serum glucose ratios, consistent with impaired glucose transport across the blood brain barrier, are associated with cerebral metabolic distress and increased mortality after severe brain injury.

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

INTRODUCTION: We 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). METHODS: We 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). RESULTS: Daily 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. CONCLUSIONS: In 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.

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.

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, PbtO(2) and microdialysis. The authors compared mean arterial blood pressure, ICP, cerebral perfusion pressure, PbtO(2), 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 PbtO(2) 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.

Prevention of shivering during therapeutic temperature modulation: the Columbia anti-shivering protocol.

BACKGROUND: As 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. METHODS: All 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. RESULTS: We 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. CONCLUSIONS: A 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.

Anemia is associated with metabolic distress and brain tissue hypoxia after subarachnoid hemorrhage.

BACKGROUND: Anemia is frequently encountered in critically ill patients and adversely affects cerebral oxygen delivery and brain tissue oxygen (PbtO2). The objective of this study is to assess whether there is an association between anemia and metabolic distress or brain tissue hypoxia in patients with subarachnoid hemorrhage. METHODS: Retrospective study was conducted in a neurological intensive care unit in a university hospital. Patients with subarachnoid hemorrhage that underwent multimodality monitoring with intracranial pressure, PbtO2 and microdialysis were analyzed. The relationships between hemoglobin (Hb) concentrations and brain tissue hypoxia (PbtO2 < or = 15 mmHg) and metabolic distress (lactate/pyruvate ratio > or =40) were analyzed with general linear models of logistic function for dichotomized outcomes utilizing generalized estimating equations. RESULTS: A total of 359 matched neuromonitoring hours and Hb measurements were analyzed from 34 consecutive patients. The median hemoglobin was 9.7 g/dl (interquartile range 8.8-10.5). After adjusting for significant covariates, reduced hemoglobin concentration was associated with a progressively increased risk of brain tissue hypoxia (adjusted OR 1.7 [1.1-2.4]; P = 0.01 for every unit decrease). Also after adjusting for significant covariates, hemoglobin concentrations below 9 g/dl and between 9.1 and 10 g/dl were associated with an increased risk of metabolic distress as compared to concentrations between 10.1 and 11 g/dl (adjusted OR 3.7 [1.5-9.4]; P = 0.004 for Hb < or = 9 g/dl and adjusted OR 1.9 [1.1-3.3]; P = 0.03 for Hb 9.1-10 g/dl). CONCLUSIONS: Anemia is associated with a progressively increased risk of cerebral metabolic distress and brain tissue hypoxia after subarachnoid hemorrhage.

Systemic glucose and brain energy metabolism after subarachnoid hemorrhage.

BACKGROUND: Brain energy metabolic crisis (MC) and lactate-pyruvate ratio (LPR) elevations have been linked to poor outcome in comatose patients. We sought to determine if MC and LPR elevations after subarachnoid hemorrhage (SAH) are associated with acute reductions in serum glucose. METHODS: Twenty-eight consecutive comatose SAH patients that underwent multimodality monitoring with intracranial pressure and microdialysis were studied. MC was defined as lactate/pyruvate ratio (LPR) > or = 40 and brain glucose < 0.7 mmol/l. Time-series data were analyzed using a multivariable general linear model with a logistic link function for dichotomized outcomes. RESULTS: Multimodality monitoring included 3,178 h of observation (mean 114 +/- 65 h per patient). In exploratory analysis, serum glucose significantly decreased from 8.2 +/- 1.8 mmol/l (148 mg/dl) 2 h before to 6.9 +/- 1.9 mmol/l (124 mg/dl) at the onset of MC (P < 0.001). Reductions in serum glucose of 25% or more were significantly associated with new onset MC (adjusted odds ratio [OR] 3.6, 95% confidence interval [CI] 2.2-6.0). Acute reductions in serum glucose of 25% or more were also significantly associated with an LPR rise of 25% or more (adjusted OR 1.6, 95% CI 1.1-2.4). All analyses were adjusted for significant covariates including Glasgow Coma Scale and cerebral perfusion pressure. CONCLUSIONS: Acute reductions in serum glucose, even to levels within the normal range, may be associated with brain energy metabolic crisis and LPR elevation in poor-grade SAH patients.

Neuromonitoring in intensive care: focus on microdialysis and its nursing implications.

Neuromonitoring with the microdialysis technique is now being utilized at the bedside. Cerebral metabolism monitoring enables identification of clinical events hours or even days before clinical examination changes, providing clinical staff an opportunity for earlier intervention. Cerebral microdialysis also allows clinicians to evaluate the impact of therapeutics on cerebral metabolism and certain metabolic patterns, which can trigger specific alerts and/or clinical protocols. Cerebral metabolism monitoring through microdialysis can guide clinicians to institute therapeutic measures that prevent the occurrence of secondary injury. This article focuses on the state-of-the-art application of cerebral microdialysis, the rationale for its use, and the nursing implications of this technique.

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.

Nursing priorities in caring for patients with intracerebral hemorrhage.

Patients afflicted with intracerebral hemorrhage (ICH) experience potentially devastating neurological sequelae; current therapy for ICH remains supportive. However, hemostatic therapy with recombinant activated factor VIIa holds promise for decreasing the morbidity and mortality of patients following an ICH. Nurses who are the responsible clinicians at the bedside often find it challenging to care for these patients. This article discusses the priorities that nurses need to determine as they balance the overall needs of the patient, incorporating recombinant activated factor VIIa as a new treatment for ICH.

Shivering management during therapeutic temperature modulation: nurses' perspective.

Therapeutic temperature modulation, which incorporates mild hypothermia and maintenance of normothermia, is being used to manage patients resuscitated after cardiac arrest. Methods of modulating temperature include intravenous infusion of cold fluids and surface or endovascular cooling. During this therapy, the shiver response is activated as a defense mechanism in response to an altered set-point temperature and causes metabolic and hemodynamic stress for patients. Recognition of shivering according to objective and subjective assessments is vital for early detection of the condition. Once shivering is detected, treatment is imperative to avoid deleterious effects. The Bedside Shivering Assessment Scale can be used to determine the efficacy of interventions intended to blunt thermoregulatory defenses and can provide continual evaluation of patients' responses to the interventions. Nurses' knowledge and understanding of the harmful effects of shivering are important to effect care and prevent injury associated with uncontrolled shivering.

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.

Predictors and clinical implications of shivering during therapeutic normothermia.

BACKGROUND: Shivering during induced normothermia (IN) remains a therapeutic limitation. We investigated potential risk factors and clinical implications of shivering during IN. METHODS: Post hoc analysis was performed on 24 patients enrolled in a clinical trial of an automated surface cooling system to achieve IN. Hyponatremia was defined as serum levels <136 mmol/L and hypomagnesaemia as levels <1.5 mg/dL. Continuous heat energy transfer (kcal/h) was averaged hourly. Glasgow Coma Scale (GCS) scores were recorded every 2 h. Shivering status was documented hourly. Mixed effects modeling was used to determine clinical measures associated with shivering. Generalized estimating equation (GEE) models were used to compare baseline-adjusted repeated-measures GCS scores. RESULTS: About of 24 (39%) patients demonstrated shivering. Shivering was associated with men (67% vs. 21%, P = 0.03), hyponatremia (44% vs. 7%, P = 0.03), and hypomagnesaemia (56% vs. 7%, P = 0.02). The average kcal/h (158 +/- 645 kcal/h vs. 493 +/- 645 kcal/h, P = 0.03) was greater in shivering patients. Shivering was positively associated with increases in heart rate (P < 0.001), respiratory rate (P < 0.001), and kcal/h (P < 0.001). Non-shivering patients showed a greater increase from baseline GCS (GEE, P = 0.02) at 24 h. No differences in sedative doses or fever burden were noted between shiverers and non-shiverers. CONCLUSIONS: Men, hyponatremia, and hypomagnesaemia may predispose febrile patients treated with IN to shivering. Shivering dramatically increases the amount of heat transfer required to maintain normothermia, and may be associated with adverse effects on level of consciousness.

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 > or =38.3 degrees 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 degrees 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 degrees -hrs, p = .001). Arctic Sun-treated patients also spent less percent time febrile (T > or =38.3 degrees C, 8% vs. 42%, p < .001), spent more percent time normothermic (T < or =37.2 degrees 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.