Optimizing Mean Arterial Pressure in Acutely Comatose Patients Using Cerebral Autoregulation Multimodal Monitoring With Near-Infrared Spectroscopy.

OBJECTIVES: This study investigated whether comatose patients with greater duration and magnitude of clinically observed mean arterial pressure outside optimal mean arterial blood pressure have worse outcomes than those with mean arterial blood pressure closer to optimal mean arterial blood pressure calculated by bedside multimodal cerebral autoregulation monitoring using near-infrared spectroscopy. DESIGN: Prospective observational study. SETTING: Neurocritical Care Unit of the Johns Hopkins Hospital. SUBJECTS: Acutely comatose patients secondary to brain injury. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The cerebral oximetry index was continuously monitored with near-infrared spectroscopy for up to 3 days. Optimal mean arterial blood pressure was defined as that mean arterial blood pressure at the lowest cerebral oximetry index (nadir index) for each 24-hour period of monitoring. Kaplan-Meier analysis and proportional hazard regression models were used to determine if survival at 3 months was associated with a shorter duration of mean arterial blood pressure outside optimal mean arterial blood pressure and the absolute difference between clinically observed mean arterial blood pressure and optimal mean arterial blood pressure. A total 91 comatose patients were enrolled in the study. The most common etiology was intracerebral hemorrhage. Optimal mean arterial blood pressure could be calculated in 89 patients (97%), and the median optimal mean arterial blood pressure was 89.7 mm Hg (84.6-100 mm Hg). In multivariate proportional hazard analysis, duration outside optimal mean arterial blood pressure of greater than 80% of monitoring time (adjusted hazard ratio, 2.13; 95% CI, 1.04-4.41; p = 0.04) and absolute difference between clinically observed mean arterial blood pressure and optimal mean arterial blood pressure of more than 10 mm Hg (adjusted hazard ratio, 2.44; 95% CI, 1.21-4.92; p = 0.013) were independently associated with mortality at 3 months, after adjusting for brain herniation, admission Glasgow Coma Scale, duration on vasopressors and midline shift at septum. CONCLUSIONS: Comatose neurocritically ill adults with an absolute difference between clinically observed mean arterial blood pressure and optimal mean arterial blood pressure greater than 10 mm Hg and duration outside optimal mean arterial blood pressure greater than 80% had increased mortality at 3 months. Noninvasive near-infrared spectroscopy-based bedside calculation of optimal mean arterial blood pressure is feasible and might be a promising tool for cerebral autoregulation oriented-therapy in neurocritical care patients.

Outcomes of Tracheostomy With Concomitant and Delayed Percutaneous Endoscopic Gastrostomy in the Neuroscience Critical Care Unit.

BACKGROUND: In patients with severe neurologic conditions, percutaneous endoscopic gastrostomy (PEG) is typically performed either alone or with a tracheostomy. The characteristics and outcomes of patients receiving PEG concomitantly with a tracheostomy (CTPEG) and those receiving delayed PEG (DPEG) after a tracheostomy were compared. METHODS: Retrospective cohort study in a 24-bed neuroscience critical care unit (NCCU) at a tertiary care hospital. Consecutive patients admitted to the NCCU from April 2007 to July 2013 who underwent percutaneous tracheostomy and gastrostomy by the percutaneous tracheostomy team were included and grouped according to the timing of PEG placement: CTPEG versus DPEG. RESULTS: Of the 290 patients, 234 (81%) received CTPEG. Demographic and clinical characteristics were similar among the 2 groups except for a lower median (interquartile range [IQR]) body mass index (BMI; 27 [22.67-31.60] versus 30.8 [24.55-40.06], P = .017) and lower rate of acute respiratory distress syndrome (3.85% vs 10.71%, P = .048) in the CTPEG cohort. Furthermore, 59% of CTPEG cohort were neurology patients while 63% of DPEG were neurosurgery patients, P = .004. Primary outcomes showed shorter mean NCCU length of stay (LOS; 25 [12] vs 33 [17] days, P < .001) and median hospital LOS (32 [25-43] vs 37 [31-56] days, P = .002) for the CTPEG cohort. Secondary outcomes showed higher predischarge prealbumin levels (15.6 [7.75] vs 11.58 [5.41], P = .021) and lower median overall hospital cost (US$123 860.20 [US$99 024-US$168 713.40] vs US$159 633.50 [US$121 312-US$240 213.10], P = .0003) in the CTPEG group. Anatomic contraindications were the most common reason for DPEG (30%). CONCLUSIONS: Among institutions with a tracheostomy team, the practice of tracheostomy with concomitant PEG placement may be considered as feasible as delayed PEG in carefully selected neurocritically ill patients with possible advantages of overall shorter NCCU and hospital LOS, higher predischarge prealbumin, and lower hospital costs. These findings may aid in decisions regarding the timing of PEG placement in the NCCU. Further prospective studies are warranted.

Correction to: Intraoperative cerebral oximetry-based management for optimizing perioperative outcomes: a meta-analysis of randomized controlled trials.

In the article entitled "Intraoperative cerebral oximetry-based management for optimizing perioperative outcomes: a meta-analysis of randomized controlled trials" Can J Anesth 2018; 65: 529-42, we wish to clarify the following items.

Determining the Upper and Lower Limits of Cerebral Autoregulation With Cerebral Oximetry Autoregulation Curves: A Case Series.

OBJECTIVE: Critical care guidelines recommend a single target value for mean arterial blood pressure in critically ill patients. However, growing evidence regarding cerebral autoregulation challenges this concept and supports individualizing mean arterial blood pressure targets to prevent brain and kidney hypo- or hyperperfusion. Regional cerebral oxygen saturation derived from near-infrared spectroscopy is an acceptable surrogate for cerebral blood flow and has been validated to measure cerebral autoregulation. This study suggests a novel mechanism to construct autoregulation curves based on near-infrared spectroscopy-measured cerebral oximetry. DESIGN: Case-series study. SETTING: Neurocritical care unit in a tertiary medical center. PATIENTS: Patients with acute neurologic injury and Glasgow coma scale score less than or equal to 8. MEASUREMENTS AND MAIN RESULTS: Autoregulation curves were plotted using the fractional-polynomial model in Stata after multimodal continuous monitoring of regional cerebral oxygen saturation and mean arterial blood pressure. Individualized autoregulation curves of seven patients exhibited varying upper and lower limits of autoregulation and provided useful clinical information on the autoregulation trend (curves moving to the right or left during the acute coma period). The median lower and upper limits of autoregulation were 86.5 mm Hg (interquartile range, 74-93.5) and 93.5 mm Hg (interquartile range, 83-99), respectively. CONCLUSIONS: This case-series study showed feasibility of delineating real trends of the cerebral autoregulation plateau and direct visualization of the cerebral autoregulation curve after at least 24 hours of recording without manipulation of mean arterial blood pressure by external stimuli. The integration of multimodal monitoring at the bedside with cerebral oximetry provides a noninvasive method to delineate daily individual cerebral autoregulation curves.

Antiepileptic drugs in critically ill patients.

BACKGROUND: The incidence of seizures in intensive care units ranges from 3.3% to 34%. It is therefore often necessary to initiate or continue anticonvulsant drugs in this setting. When a new anticonvulsant is initiated, drug factors, such as onset of action and side effects, and patient factors, such as age, renal, and hepatic function, should be taken into account. It is important to note that the altered physiology of critically ill patients as well as pharmacological and nonpharmacological interventions such as renal replacement therapy, extracorporeal membrane oxygenation, and target temperature management may lead to therapeutic failure or toxicity. This may be even more challenging with the availability of newer antiepileptics where the evidence for their use in critically ill patients is limited. MAIN BODY: This article reviews the pharmacokinetics and pharmacodynamics of antiepileptics as well as application of these principles when dosing antiepileptics and monitoring serum levels in critically ill patients. The selection of the most appropriate anticonvulsant to treat seizure and status epileptics as well as the prophylactic use of these agents in this setting are also discussed. Drug-drug interactions and the effect of nonpharmacological interventions such as renal replacement therapy, plasma exchange, and extracorporeal membrane oxygenation on anticonvulsant removal are also included. CONCLUSION: Optimal management of antiepileptic drugs in the intensive care unit is challenging given altered physiology, polypharmacy, and nonpharmacological interventions, and requires a multidisciplinary approach where appropriate and timely assessment, diagnosis, treatment, and monitoring plans are in place.

Intraoperative cerebral oximetry-based management for optimizing perioperative outcomes: a meta-analysis of randomized controlled trials.

PURPOSE: Although evidence from observational studies in a variety of clinical settings supports the utility of cerebral oximetry as a predictor of outcomes, prospective clinical trials thus far have reported conflicting results. This systematic review and meta-analysis was designed to evaluate the influence of management associated with intraoperative cerebral oximetry on postoperative outcomes. The primary outcome was postoperative cognitive dysfunction (POCD), with secondary outcomes that included postoperative delirium, length of intensive care unit (ICU) stay, and hospital length of stay (LOS). SOURCE: After searching the PubMed, EMBASE, Cochrane Library, Scopus, and Google Scholar databases, all randomized controlled trials (RCTs) assessing the impact of intraoperative cerebral oximetry-guided management on clinical outcomes following surgery were identified. PRINCIPAL FINDINGS: Fifteen RCTs comprising 2,057 patients (1,018 in the intervention group and 1,039 in control group) were included. Intraoperative management guided by the use of cerebral oximetry was associated with a reduction in the incidence of POCD (risk ratio [RR] 0.54; 95% confidence interval [CI], 0.33 to 0.90; P = 0.02; I2 = 85%) and a significantly shorter length of ICU stay (standardized mean difference [SMD], -0.21 hr; 95% CI, -0.37 to -0.05; P = 0.009; I2 = 48%). In addition, overall hospital LOS (SMD, -0.06 days; 95% CI, -0.18 to 0.06; P = 0.29; I2 = 0%) and incidence of postoperative delirium (RR, 0.69; 95% CI, 0.36 to 1.32; P = 0.27; I2 = 0%) were not impacted by the use of intraoperative cerebral oximetry. CONCLUSIONS: Intraoperative cerebral oximetry appears to be associated with a reduction in POCD, although this result should be interpreted with caution given the significant heterogeneity in the studies examined. Further large (ideally multicentre) RCTs are needed to clarify whether POCD can be favourably impacted by the use of cerebral oximetry-guided management.

Cerebral Autoregulation-oriented Therapy at the Bedside: A Comprehensive Review.

This comprehensive review summarizes the evidence regarding use of cerebral autoregulation-directed therapy at the bedside and provides an evaluation of its impact on optimizing cerebral perfusion and associated functional outcomes. Multiple studies in adults and several in children have shown the feasibility of individualizing mean arterial blood pressure and cerebral perfusion pressure goals by using cerebral autoregulation monitoring to calculate optimal levels. Nine of these studies examined the association between cerebral perfusion pressure or mean arterial blood pressure being above or below their optimal levels and functional outcomes. Six of these nine studies (66%) showed that patients for whom median cerebral perfusion pressure or mean arterial blood pressure differed significantly from the optimum, defined by cerebral autoregulation monitoring, were more likely to have an unfavorable outcome. The evidence indicates that monitoring of continuous cerebral autoregulation at the bedside is feasible and has the potential to be used to direct blood pressure management in acutely ill patients.

Validation of Near-Infrared Spectroscopy for Monitoring Cerebral Autoregulation in Comatose Patients.

BACKGROUND: Transcranial Doppler (TCD) noninvasively measures cerebral blood flow (CBF) velocity and is a well-studied method to monitor cerebral autoregulation (CA). Near-infrared spectroscopy (NIRS) has emerged as a promising noninvasive method to determine CA continuously by using regional cerebral oxygen saturation (rSO2) as a surrogate for CBF. Little is known about its accuracy to determine CA in patients with intracranial lesions. The purpose of this study was to assess the accuracy of rSO2-based CA monitoring with TCD methods in comatose patients with acute neurological injury. METHODS: Thirty-three comatose patients were monitored at the bedside to measure CA using both TCD and NIRS. Patients were monitored daily for up to three days from coma onset. The cerebral oximetry index (COx) was calculated as the moving correlation between the slow waves of rSO2 and mean arterial pressure (MAP). The mean velocity index (Mx) was calculated as a similar coefficient between slow waves of TCD-measured CBF velocity and MAP. Optimal blood pressure was defined as the MAP with the lowest Mx and COx. Averaged Mx and COx as well as optimal MAP, based on both Mx and COx, were compared using Pearson's correlation. Bias analysis was performed between these same CA metrics. RESULTS: The median duration of monitoring was 60 min (interquartile range [IQR] 48-78). There was a moderate correlation between the averaged values of COx and Mx (R = 0.40, p = 0.005). Similarly, there was a strong correlation between optimal MAP calculated for COx and Mx (R = 0.87, p < 0.001). Bland-Altman analysis showed moderate agreement with bias (±standard deviation) of -0.107 (±0.191) for COx versus Mx and good agreement with bias of 1.90 (±7.94) for optimal MAP determined by COx versus Mx. CONCLUSIONS: Monitoring CA with NIRS-derived COx is correlated and had good agreement with previously validated TCD-based method. These results suggest that COx may be an acceptable substitute for Mx monitoring in patients with acute intracranial injury.

Infectious Disease Risk Associated with Contaminated Propofol Anesthesia, 1989-2014(1).

Administration of propofol, the most frequently used intravenous anesthetic worldwide, has been associated with several iatrogenic infections despite its relative safety. Little is known regarding the global epidemiology of propofol-related outbreaks and the effectiveness of existing preventive strategies. In this overview of the evidence of propofol as a source of infection and appraisal of preventive strategies, we identified 58 studies through a literature search in PubMed, Embase, and Lilacs for propofol-related infections during 1989-2014. Twenty propofol-related outbreaks have been reported, affecting 144 patients and resulting in 10 deaths. Related factors included reuse of syringes for multiple patients and prolonged exposure to the environment when vials were left open. The addition of antimicrobial drugs to the emulsion has been instituted in some countries, but outbreaks have still occurred. There remains a lack of comprehensive information on the effectiveness of measures to prevent future outbreaks.

Abnormal movements in critical care patients with brain injury: a diagnostic approach.

Abnormal movements are frequently encountered in patients with brain injury hospitalized in intensive care units (ICUs), yet characterization of these movements and their underlying pathophysiology is difficult due to the comatose or uncooperative state of the patient. In addition, the available diagnostic approaches are largely derived from outpatients with neurodegenerative or developmental disorders frequently encountered in the outpatient setting, thereby limiting the applicability to inpatients with acute brain injuries. Thus, we reviewed the available literature regarding abnormal movements encountered in acutely ill patients with brain injuries. We classified the brain injury into the following categories: anoxic, vascular, infectious, inflammatory, traumatic, toxic-metabolic, tumor-related and seizures. Then, we identified the abnormal movements seen in each category as well as their epidemiologic, semiologic and clinicopathologic correlates. We propose a practical paradigm that can be applied at the bedside for diagnosing abnormal movements in the ICU. This model seeks to classify observed abnormal movements in light of various patient-specific factors. It begins with classifying the patient's level of consciousness. Then, it integrates the frequency and type of each movement with the availability of ancillary diagnostic tests and the specific etiology of brain injury.

Development and validation of a quality-of-life questionnaire for mechanically ventilated ICU patients.

OBJECTIVE: To develop and validate a new instrument for measuring health-related quality of life in mechanically ventilated patients in the ICU. DESIGN: Expert panel consensus and a prospective longitudinal survey. SETTING: Urban, academic, tertiary care medical center. PATIENTS: One hundred fifteen awake, mechanically ventilated, ICU patients who either received a tracheostomy or remained endotracheally intubated. INTERVENTIONS: A new quality-of-life instrument was developed and validated by using pilot study data; informal interviews of patients, families, and nurses; expert panel consensus; and item analyses. The new instrument was used to measure quality of life at three time points (5 d, 10 d, and 15 d after intubation). MEASUREMENTS AND MAIN RESULTS: A new 12-item quality-of-life questionnaire for mechanically ventilated patients was developed. Patients' responses to the quality-of-life questionnaire revealed moderate-to-high correlations with EuroQol scores (r = -0.4 to -0.9) and the EuroQol Visual Analog Scale (r = 0.6-0.9) across the three times and a moderate correlation with the Sequential Organ Failure Assessment tool (r = 0.5) at 10 days after intubation. Cronbach α ranged from 0.80 to 0.94 across the three times. The quality-of-life questionnaire for mechanically ventilated patients was responsive to changes in treatment modalities (tracheostomy vs no tracheostomy and early vs late tracheostomy demarcated by 10 d of intubation). Exploratory factor analysis revealed that this instrument was unidimensional in nature. CONCLUSIONS: The new quality-of-life questionnaire for mechanically ventilated patients is valid and can reliably measure quality of life in mechanically ventilated ICU patients. It may provide clinicians with an accurate assessment of patients' quality of life and facilitate optimal decision making regarding patients' ICU plan of care.

Restrictive and liberal red cell transfusion strategies in adult patients: reconciling clinical data with best practice.

Red blood cell (RBC) transfusion guidelines correctly promote a general restrictive transfusion approach for anemic hospitalized patients. Such recommendations have been derived from evaluation of specific patient populations, and it is important to recognize that engaging a strict guideline approach has the potential to incur harm if the clinician fails to provide a comprehensive review of the patient's physiological status in determining the benefit and risks of transfusion. We reviewed the data in support of a restrictive or a more liberal RBC transfusion practice, and examined the quality of the datasets and manner of their interpretation to provide better context by which a physician can make a sound decision regarding RBC transfusion therapy. Reviewed studies included PubMed-cited (1974 to 2013) prospective randomized clinical trials, prospective subset analyses of randomized studies, nonrandomized controlled trials, observational case series, consecutive and nonconsecutive case series, and review articles. Prospective randomized clinical trials were acknowledged and emphasized as the best-quality evidence. The results of the analysis support that restrictive RBC transfusion practices appear safe in the hospitalized populations studied, although patients with acute coronary syndromes, traumatic brain injury and patients at risk for brain or spinal cord ischemia were not well represented in the reviewed studies. The lack of quality data regarding the purported adverse effects of RBC transfusion at best suggests that restrictive strategies are no worse than liberal strategies under the studied protocol conditions, and RBC transfusion therapy in the majority of instances represents a marker for greater severity of illness. The conclusion is that in the majority of clinical settings a restrictive RBC transfusion strategy is cost-effective, reduces the risk of adverse events specific to transfusion, and introduces no harm. In anemic patients with ongoing hemorrhage, with risk of significant bleeding, or with concurrent ischemic brain, spinal cord, or myocardium, the optimal hemoglobin transfusion trigger remains unknown. Broad-based adherence to guideline approaches of therapy must respect the individual patient condition as interpreted by comprehensive clinical review.

Difficult airway response team: a novel quality improvement program for managing hospital-wide airway emergencies.

BACKGROUND: Difficult airway cases can quickly become emergencies, increasing the risk of life-threatening complications or death. Emergency airway management outside the operating room is particularly challenging. METHODS: We developed a quality improvement program-the Difficult Airway Response Team (DART)-to improve emergency airway management outside the operating room. DART was implemented by a team of anesthesiologists, otolaryngologists, trauma surgeons, emergency medicine physicians, and risk managers in 2005 at The Johns Hopkins Hospital in Baltimore, Maryland. The DART program had 3 core components: operations, safety, and education. The operations component focused on developing a multidisciplinary difficult airway response team, standardizing the emergency response process, and deploying difficult airway equipment carts throughout the hospital. The safety component focused on real-time monitoring of DART activations and learning from past DART events to continuously improve system-level performance. This objective entailed monitoring the paging system, reporting difficult airway events and DART activations to a Web-based registry, and using in situ simulations to identify and mitigate defects in the emergency airway management process. The educational component included development of a multispecialty difficult airway curriculum encompassing case-based lectures, simulation, and team building/communication to ensure consistency of care. Educational materials were also developed for non-DART staff and patients to inform them about the needs of patients with difficult airways and ensure continuity of care with other providers after discharge. RESULTS: Between July 2008 and June 2013, DART managed 360 adult difficult airway events comprising 8% of all code activations. Predisposing patient factors included body mass index >40, history of head and neck tumor, prior difficult intubation, cervical spine injury, airway edema, airway bleeding, and previous or current tracheostomy. Twenty-three patients (6%) required emergent surgical airways. Sixty-two patients (17%) were stabilized and transported to the operating room for definitive airway management. There were no airway management-related deaths, sentinel events, or malpractice claims in adult patients managed by DART. Five in situ simulations conducted in the first program year improved DART's teamwork, communication, and response times and increased the functionality of the difficult airway carts. Over the 5-year period, we conducted 18 airway courses, through which >200 providers were trained. CONCLUSIONS: DART is a comprehensive program for improving difficult airway management. Future studies will examine the comparative effectiveness of the DART program and evaluate how DART has impacted patient outcomes, operational efficiency, and costs of care.

Optimizing Communication in Mechanically Ventilated Patients.

PURPOSE: To describe the types of talking tracheostomy tubes available, present four case studies of critically ill patients who used a specialized tracheostomy tube to improve speech, discuss their advantages and disadvantages, propose patient selection criteria, and provide practical recommendations for medical care providers. METHODS: Retrospective chart review of patients who underwent tracheostomy in 2010. RESULTS: Of the 220 patients who received a tracheostomy in 2010, 164 (74.55%) received a percutaneous tracheostomy and 56 (25.45%) received an open tracheostomy. Among the percutaneous tracheostomy patients, speech-language pathologists were consulted on 113 patients, 74 of whom were on a ventilator. Four of these 74 patients received a talking tracheostomy tube, and all four were able to speak successfully while on the mechanical ventilator even though they were unable to tolerate cuff deflation. CONCLUSIONS: Talking tracheostomy tubes allow patients who are unable to tolerate-cuff deflation to achieve phonation. Our experience with talking tracheostomy tubes suggests that clinicians should consider their use for patients who cannot tolerate cuff deflation.

Exploring quality of life in critically ill tracheostomy patients: a pilot study.

BACKGROUND: Tracheostomies are performed to improve health-related quality of life (QOL) in patients requiring prolonged mechanical ventilation. As the lengths of stay in intensive care units (ICU) increase and higher rates of tracheostomies are becoming more prevalent, issues regarding patient perceptions of their own prognoses and outcomes after tracheostomy can considerably impact QOL and in turn their care and recovery. Whether tracheostomy improves QOL, however, has not been studied adequately. Current studies investigating QOL have been limited to pre- and post-ICU admission, have relied on surrogate measures such as clinical outcomes and proxy reports, and have used inadequate instruments, failing to capture all domains of QOL. Studies using a robust instrument to investigate QOL in the ICU before and after tracheostomy are lacking. PURPOSE: To explore the feasibility of assessing patient-reported QOL of mechanically ventilated ICU patients with a tracheostomy. METHODS: A prospective longitudinal pilot study was conducted in awake and interactive patients who were mechanically ventilated in an ICU using a modified version of the University of Washington QOL Questionnaire. Data were collected at three measurement time points--Time 0 (T0), Time 1 (T1), and Time 2 (T2)--five days apart. The QOL scores were compared between patients who received a tracheostomy and those who did not, as well as between those who received a tracheostomy before and after ten days of intubation. RESULTS: The modified University of Washington Quality of Life (UWQOL) questionnaire was easily administered by one person. Patients were able to answer all the questions by writing or pointing at the answer choices with either an endotracheal or a tracheostomy tube in place. The mean time to complete the questionnaire was 7.5 minutes. QOL scores ranging from 0 to 800 were administered. Pain and speech were the most important domains contributing to QOL. The median QOL scores were 242 at T0 and T1, and 383 at T2. There was a significant difference in the median QOL scores between those who received a tracheostomy (458) and those who remained endotracheally intubated (175) at T2. Similarly, patients who received early tracheostomy reached a higher QOL score by T1 compared to those who did not (417 vs. 267). CONCLUSIONS: This pilot study demonstrates that a modified questionnaire to assess QOL in patients with prolonged mechanical ventilation is feasible, and useful in capturing artificial airway-related QOL. Further studies should evaluate the utility of this tool in a larger study.

Comparison of equivolume, equiosmolar solutions of mannitol and hypertonic saline with or without furosemide on brain water content in normal rats.

BACKGROUND: Mannitol and hypertonic saline (HS) are used by clinicians to reduce brain water and intracranial pressure and have been evaluated in a variety of experimental and clinical protocols. Administering equivolume, equiosmolar solutions in healthy animals could help produce fundamental data on water translocation in uninjured tissue. Furthermore, the role of furosemide as an adjunct to osmotherapy remains unclear. METHODS: Two hundred twenty isoflurane-anesthetized rats were assigned randomly to receive equivolume normal saline, 4.2% HS (1,368 mOsm/L 25% mannitol (1,375 mOsm/L), normal saline plus furosemide (8 mg/kg), or 4.2% HS plus furosemide (8 mg/kg) over 45 min. Rats were killed at 1, 2, 3, and 5 h after completion of the primary infusion. Outcome measurements included body weight; urinary output; serum and urinary osmolarity and electrolytes; and brain, lung, skeletal muscle, and small bowel water content. RESULTS: In the mannitol group, the mean water content of brain tissue during the experiment was 78.0% (99.3% CI, 77.9-78.2%), compared to results from the normal saline (79.3% [99.3% CI, 79.1-79.5%]) and HS (78.8% [99.3% CI, 78.6-78.9%]) groups (P < 0.001), whereas HS plus furosemide yielded 78.0% (99.3% CI, 77.8-78.2%) (P = 0.917). After reaching a nadir at 1 h, brain water content increased at similar rates for mannitol (0.27%/h [99.3% CI, 0.14-0.40%/h]) and HS (0.27%/h [99.3% CI, 0.17-0.37%/h]) groups (P = 0.968). CONCLUSIONS: When compared to equivolume, equiosmolar administration of HS, mannitol reduced brain water content to a greater extent over the entire course of the 5-h experiment. When furosemide was added to HS, the brain-dehydrating effect could not be distinguished from that of mannitol.

Status epilepticus: an update.

Status epilepticus (SE) still results in significant mortality and morbidity. Whereas mortality depends mainly on the age of the patient as well as the cause, morbidity is often due to the myriad of complications that occur during prolonged admission to an intensive care environment. Although SE is a clinical diagnosis in most cases (convulsant), its treatment requires support by continuous electroencephalographic recording to ensure cessation of potential nonconvulsive elements of SE. Treatment has recently changed to incorporate four stages and must be initiated at the earliest possible time.

Infarct volume after hyperacute infusion of hypertonic saline in a rat model of acute embolic stroke.

INTRODUCTION: Hypertonic saline (HS) can treat cerebral edema arising from a number of pathologic conditions. However, physicians are reluctant to use it during the first 24 h after stroke because of experimental evidence that it increases infarct volume when administered early after reperfusion. Here, we determined the effect of HS on infarct size in an embolic clot model without planned reperfusion. METHODS: A clot was injected into the internal carotid artery of male Wistar rats to reduce perfusion in the middle cerebral artery territory to less than 40 % of baseline, as monitored by laser-Doppler flowmetry. After 25 min, rats were randomized to receive 10 mL/kg of 7.5 % HS (50:50 chloride:acetate) or normal saline (NS) followed by a 0.5 mL/h infusion of the same solution for 22 h. RESULTS: Infarct volume was similar between NS and HS groups (in mm(3): cortex 102 ± 65 mm(3) vs. 93 ± 49 mm(3), p = 0.72; caudoputamenal complex 15 ± 9 mm(3) vs. 21 ± 14, p = 0.22; total hemisphere 119 ± 76 mm(3) vs. 114 ± 62, p = 0.88, respectively). Percent water content was unchanged in the infarcted hemisphere (NS 81.6 ± 1.5 %; HS 80.7 ± 1.3 %, p = 0.16), whereas the HS-treated contralateral hemisphere was significantly dehydrated (NS 79.4 ± 0.8 %; HS 77.5 ± 0.8 %, p < 0.01). CONCLUSIONS: HS reduced contralateral hemispheric water content but did not affect ipsilateral brain water content when compared to NS. Infarct volume was unaffected by HS administration at all evaluated locations.

Embolic occlusion of internal carotid artery in conscious rats: Immediate effects of cerebral ischemia.

In most preclinical models of focal ischemic stroke, vascular occlusion is performed under general anesthesia. However, anesthetic agents exert confounding effects on mean arterial blood pressure (MABP), cerebrovascular tone, oxygen demand, and neurotransmitter receptor transduction. Moreover, the majority of studies do not use a blood clot, which more fully models embolic stroke. Here, we developed a blood clot injection model to produce large cerebral artery ischemia in unanesthetized rats. Under isoflurane anesthesia, an indwelling catheter was implanted in the internal carotid artery via a common carotid arteriotomy and preloaded with a 0.38-mm-diameter clot of 1.5, 3, or 6 cm length. After discontinuing anesthesia, the rat was returned to a home cage where it regained normal mobility, grooming, eating activity, and a stable recovery of MABP. One hour later, the clot was injected over a 10-s period and the rats were observed for 24 h. Clot injection produced a brief period of irritability, then 15-20 min of complete inactivity, followed by lethargic activity at 20-40 min, ipsilateral deviation of the head and neck at 1-2 h, and limb weakness and circling at 2-4 h. Neurologic deficits, elevated MABP, infarct volume, and increased hemisphere water content varied directly with clot size. Mortality after 6-cm clot injection (53%) was greater than that after 1.5-cm (10%) or 3-cm (20%) injection. Combined non-survivor groups had the greatest MABP, infarct volume, and water content. Among all groups, the pressor response correlated with infarct volume. The coefficient of variation of infarct volume with the 3-cm clot was less than that in published studies with the filament or standard clot models, and therefore may provide stronger statistical power for stroke translational studies. The more severe outcomes from the 6-cm clot model may be useful for the study of malignant stroke.