Hemodynamic Management in the Prevention and Treatment of Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage.

One of the most serious complications after subarachnoid hemorrhage (SAH) is delayed cerebral ischemia, the cause of which is multifactorial. Delayed cerebral ischemia considerably worsens neurological outcome and increases the risk of death. The targets of hemodynamic management of SAH have widely changed over the past 30 years. Hypovolemia and hypotension were favored prior to the era of early aneurysmal surgery but were subsequently replaced by the use of hypervolemia and hypertension. More recently, the concept of goal-directed therapy targeting euvolemia, with or without hypertension, is gaining preference. Despite the evolving concepts and the vast literature, fundamental questions related to hemodynamic optimization and its effects on cerebral perfusion and patient outcomes remain unanswered. In this review, we explain the rationale underlying the approaches to hemodynamic management and provide guidance on contemporary strategies related to fluid administration and blood pressure and cardiac output manipulation in the management of SAH.

Guidelines for the Neurocritical Care Management of Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: The neurointensive care management of patients with aneurysmal subarachnoid hemorrhage (aSAH) is one of the most critical components contributing to short-term and long-term patient outcomes. Previous recommendations for the medical management of aSAH comprehensively summarized the evidence based on consensus conference held in 2011. In this report, we provide updated recommendations based on appraisal of the literature using the Grading of Recommendations Assessment, Development, and Evaluation methodology. METHODS: The Population/Intervention/Comparator/Outcome (PICO) questions relevant to the medical management of aSAH were prioritized by consensus from the panel members. The panel used a custom-designed survey instrument to prioritize clinically relevant outcomes specific to each PICO question. To be included, the study design qualifying criteria were as follows: prospective randomized controlled trials (RCTs), prospective or retrospective observational studies, case-control studies, case series with a sample larger than 20 patients, meta-analyses, restricted to human study participants. Panel members first screened titles and abstracts, and subsequently full text review of selected reports. Data were abstracted in duplicate from reports meeting inclusion criteria. Panelists used the Grading of Recommendations Assessment, Development, and Evaluation Risk of Bias tool for assessment of RCTs and the "Risk of Bias In Nonrandomized Studies - of Interventions" tool for assessment of observational studies. The summary of the evidence for each PICO was presented to the full panel, and then the panel voted on the recommendations. RESULTS: The initial search retrieved 15,107 unique publications, and 74 were included for data abstraction. Several RCTs were conducted to test pharmacological interventions, and we found that the quality of evidence for nonpharmacological questions was consistently poor. Five PICO questions were supported by strong recommendations, one PICO question was supported by conditional recommendations, and six PICO questions did not have sufficient evidence to provide a recommendation. CONCLUSIONS: These guidelines provide recommendations for or against interventions proven to be effective, ineffective, or harmful in the medical management of patients with aSAH based on a rigorous review of the available literature. They also serve to highlight gaps in knowledge that should guide future research priorities. Despite improvements in the outcomes of patients with aSAH over time, many important clinical questions remain unanswered.

Effect of prehospital induction of mild hypothermia on survival and neurological status among adults with cardiac arrest: a randomized clinical trial.

IMPORTANCE: Hospital cooling improves outcome after cardiac arrest, but prehospital cooling immediately after return of spontaneous circulation may result in better outcomes. OBJECTIVE: To determine whether prehospital cooling improves outcomes after resuscitation from cardiac arrest in patients with ventricular fibrillation (VF) and without VF. DESIGN, SETTING, AND PARTICIPANTS: A randomized clinical trial that assigned adults with prehospital cardiac arrest to standard care with or without prehospital cooling, accomplished by infusing up to 2 L of 4°C normal saline as soon as possible following return of spontaneous circulation. Adults in King County, Washington, with prehospital cardiac arrest and resuscitated by paramedics were eligible and 1359 patients (583 with VF and 776 without VF) were randomized between December 15, 2007, and December 7, 2012. Patient follow-up was completed by May 1, 2013. Nearly all of the patients resuscitated from VF and admitted to the hospital received hospital cooling regardless of their randomization. MAIN OUTCOMES AND MEASURES: The primary outcomes were survival to hospital discharge and neurological status at discharge. RESULTS: The intervention decreased mean core temperature by 1.20°C (95% CI, -1.33°C to -1.07°C) in patients with VF and by 1.30°C (95% CI, -1.40°C to -1.20°C) in patients without VF by hospital arrival and reduced the time to achieve a temperature of less than 34°C by about 1 hour compared with the control group. However, survival to hospital discharge was similar among the intervention and control groups among patients with VF (62.7% [95% CI, 57.0%-68.0%] vs 64.3% [95% CI, 58.6%-69.5%], respectively; P = .69) and among patients without VF (19.2% [95% CI, 15.6%-23.4%] vs 16.3% [95% CI, 12.9%-20.4%], respectively; P = .30). The intervention was also not associated with improved neurological status of full recovery or mild impairment at discharge for either patients with VF (57.5% [95% CI, 51.8%-63.1%] of cases had full recovery or mild impairment vs 61.9% [95% CI, 56.2%-67.2%] of controls; P = .69) or those without VF (14.4% [95% CI, 11.3%-18.2%] of cases vs 13.4% [95% CI,10.4%-17.2%] of controls; P = .30). Overall, the intervention group experienced rearrest in the field more than the control group (26% [95% CI, 22%-29%] vs 21% [95% CI, 18%-24%], respectively; P = .008), as well as increased diuretic use and pulmonary edema on first chest x-ray, which resolved within 24 hours after admission. CONCLUSION AND RELEVANCE: Although use of prehospital cooling reduced core temperature by hospital arrival and reduced the time to reach a temperature of 34°C, it did not improve survival or neurological status among patients resuscitated from prehospital VF or those without VF. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00391469.

The Postoperative Airway Compromise Score-First Steps to Developing a Postoperative Tool for the Assessment of Upper Airway-Related Complications Following Anterior Cervical Spine Surgery.

BACKGROUND: Acute upper airway compromise is a rare but catastrophic complication after anterior cervical discectomy and fusion. This study aims to develop a score to identify patients at risk of acute postoperative airway compromise (PAC). METHODS: Potential risk factors for acute PAC were selected by a modified Delphi process. Ten patients with acute PAC were identified of 1466 patients who underwent elective anterior cervical discectomy and fusion between July 2014 and May 2019. A comparison group was created by a randomized selection process (non-PAC group). Factors associated with PAC and a P value of < 0.10 were entered into a logistic regression model and coefficients contributed to each risk factor's overall score. Calibration of the model was evaluated using the Hosmer-Lemeshow goodness-of-fit test. Quantitative discrimination was calculated, and the final model was internally validated with bootstrap sampling. RESULTS: We identified 18 potential risk factors from our Delphi process, of which 6 factors demonstrated a significant association with airway compromise: age >65 years, current smoking status, American Society of Anesthesiologists class >2, history of a bleeding disorder, surgery of upper subaxial cervical spine (above C4), and duration of surgery >179 minutes. The final prediction model included 5 predictors with very strong performance characteristics. These 5 factors formed the PAC score, with a range from 0 to 100. A score of 20 yielded the greatest balance of sensitivity (80%) and specificity (88%). CONCLUSIONS: The acute PAC score demonstrates strong performance characteristics. The PAC score might help identify patients at risk of upper airway compromise caused by surgical site abnormalities.

Targeting brain tissue oxygenation in traumatic brain injury.

The management of patients with traumatic brain injury has evolved in the last several years, due to the introduction of new, invasive monitoring devices. The ability to monitor parameters other than measurements related to pressures has generated substantial interest. Brain tissue oxygenation monitoring has been consistently shown to provide prognostic information, as indicated by poor prognosis associated with low brain tissue oxygen values. Furthermore, various physiologic manipulations, including increasing the P(aO(2)), have been associated with an increase in brain tissue oxygenation. Whether brain-oxygenation-guided therapy results in improvement in outcomes is debatable. Retrospective studies suggest benefit, while prospective studies have shown a higher intensity of therapeutic interventions with no outcome differences. Data from high quality randomized trials are necessary to determine if brain-oxygenation-guided therapy is beneficial. An oxygen challenge (transient increase in F(IO(2)) to 0.6 up to 1.0) to assess the responsiveness of the monitoring and ascertain the presence of technical malfunction is an accepted practice.

Occurrence and complications of tracheal reintubation in critically ill adults.

BACKGROUND: Timing and preparation for tracheal extubation are as critical as the initial intubation. There are limited data on specific strategies for a planned extubation. The extent to which the difficult airway at reintubation contributes to patient morbidity is unknown. The aim of the present study was to describe the occurrence and complications of failed extubation and associated risk factors, and to estimate the mortality and morbidity associated with reintubation attempts. METHODS: Cohort study of 2,007 critically ill adult patients admitted to the ICU with an ETT. Patients were classified in 2 groups, based on the requirement for reintubation: "never reintubated" versus "≥ 1 reintubations." Baseline characteristics, ICU and hospital stay, hospital mortality, and in-patient costs were compared between patients successfully extubated and those with reintubation outside the operating room, using regression techniques. Reasons, airway management techniques, and complications of intubation and reintubation were summarized descriptively. RESULTS: 376 patients (19%) required reintubation, and 230 (11%) were reintubated within 48 hours, primarily due to respiratory failure. Patients requiring reintubation were older, more likely to be male, and had higher admission severity score. Difficult intubation and complications were similar for initial and subsequent intubation. Reintubation was associated with a 5-fold increase in the relative odds of death (adjusted odds ratio 5.86, 95% CI 3.87-8.89, P < .01), and a 2-fold increase in median ICU and hospital stay, and institutional costs. Difficult airway at reintubation was associated with higher mortality (adjusted odds ratio 2.23, 95% CI 1.01-4.93, P = .05). CONCLUSIONS: Nearly 20% of critically ill patients required out of operating room reintubation. Reintubation was associated with higher mortality, stay, and cost. Moreover, a difficult airway at reintubation was associated with higher mortality.

The association between fluid balance and outcomes after subarachnoid hemorrhage.

BACKGROUND: We sought to determine the association between early fluid balance and neurological/vital outcome of patients with subarachnoid hemorrhage. METHODS: Hospital admission, imaging, ICU and outcome data were retrospectively collected from the medical records of adult patients with aneurysmal SAH admitted to a level-1 trauma and stroke referral center during a 5-year period. Two groups were identified based on cumulative fluid balance by ICU day 3: (i) patients with a positive fluid balance (n = 221) and (ii) patients with even or negative fluid balance (n = 135). Multivariable logistic regression was used to adjust for age, Hunt-Hess and Fisher scores, mechanical ventilation and troponin elevation (>0.40 ng/ml) at ICU admission. The primary outcome was a composite of hospital mortality or new stroke. RESULTS: Patients with positive fluid balance had worse admission GCS and Hunt-Hess score, and by ICU day 3 had cumulatively received more IV fluids, but had less urine output when compared with the negative fluid balance group. There was no difference in the odds of hospital death or new stroke (adjusted OR: 1.47, 95%CI: 0.85, 2.54) between patients with positive and negative fluid balance. However, positive fluid balance was associated with increased odds of TCD vasospasm (adjusted OR 2.25, 95%CI: 1.37, 3.71) and prolonged hospital length of stay. CONCLUSIONS: Although handling of IV fluid administration was not an independent predictor of mortality or new stroke, patients with early positive fluid balance had worse clinical presentation and had greater resource use during the hospital course.

Current practices of triple-H prophylaxis and therapy in patients with subarachnoid hemorrhage.

BACKGROUND: Medical management of cerebral vasospasm following aneurysmal subarachnoid hemorrhage (SAH) includes hypertensive, hypervolemic, and hemodilution ("triple-H") therapy. However, there is little information regarding the indications and guidance used to initiate and adjust triple-H therapy. METHODS: A 43-item questionnaire was e-mailed to 375 members of the Neurocritical Care Society. Questions were designed to investigate the diagnostic approach to cerebral vasospasm and prophylactic and therapeutic administration of triple-H therapy. RESULTS: Completed surveys were received from 167 respondents (45% response proportion). Eighty-six percent of respondents worked in hospitals with neurointensive care units (NICUs). SAH patients in hospitals with a NICU had longer ICU stay (P = 0.037) and had indwelling central venous catheters for longer (P < 0.01). Centers without dedicated NICUs were more likely to induce prophylactic hypervolemia (P < 0.01). Twenty seven percent of respondents (n = 45) reported using prophylactic hypervolemia in patients with SAH, while 100% reported inducing hypervolemia for severe or symptomatic vasospasm. Twelve percent (n = 20) of respondents reported inducing prophylactic hypertension, while all reported inducing hypertension with severe or symptomatic vasospasm. Half of respondents relied on the mean arterial pressure and half on systolic blood pressure as the clinical parameter for blood pressure titration. The most widely used agents to induce hypertension were phenylephrine (48%) and norepinephrine (39%). There was little variation in the use of hemodilution therapy comparing patients with or without evidence of vasospasm. CONCLUSIONS: There are substantial differences in the administration of prophylactic triple-H, but there was high agreement on indication for therapeutic use. There was wide variability in the extent of ICU monitoring, diagnostic approach, physiologic parameters and values used as target of therapy. NICU availability was associated with more intensive monitoring. Lack of evidence and guidelines for triple-H therapy might largely explain these findings.

Open-label randomized trial of the safety and efficacy of a single dose conivaptan to raise serum sodium in patients with traumatic brain injury.

BACKGROUND: Conivaptan is an arginine-vasopressin-receptor antagonist approved for the treatment of hyponatremia. We hypothesized that administration of conivaptan to normonatremic patients with traumatic brain injury (TBI) is safe and could reduce intracranial pressure (ICP). METHODS: Open-label, randomized, controlled trial enrolling 10 subjects within 24 h of severe TBI to receive a single 20 mg dose of conivaptan (n = 5) or usual care (n = 5). The primary endpoint was the evaluation of the safety profile defined by serum sodium increases averaging >1 mEq/h when measured every 4 h and any adverse events. Secondary endpoints were 48-h serum sodium, sodium load, change in ICP, and urine output. RESULTS: Ten patients were included in the intention-to-treat analysis. Three patients (2 conivaptan, 1 usual care group) experienced brief sodium increases averaging >1 mEq/h, with no patients achieving Na >160 mEq/l. There were no drug-related serious adverse events. At 48 h, the mean sodium was 142 ± 6 mEq/l (conivaptan) and 144 ± 10 mEq/l (usual care, P = 0.71). 48-h sodium load was 819 ± 724 mEq in the conivaptan and 1,137 ± 1,165 mEq in the usual care group (P = 0.62). At 4 h, serum sodium was higher (P = 0.02) and ICP was lower (P = 0.046) in the conivaptan compared with usual care group. 24-h but not 48-h urine output was different between the two groups (P < 0.01 and P = 0.20, respectively). CONCLUSIONS: These data suggest that a single dose conivaptan is safe in non-hyponatremic patients with severe TBI and may reduce ICP. Further studies are needed to establish the effect of conivaptan on clinically relevant endpoints, and its role in the management of intracranial hypertension.

New endotracheal tubes designed to prevent ventilator-associated pneumonia: do they make a difference?

Ventilator-associated pneumonia (VAP) is a pervasive and expensive nosocomial infection that is largely related to instrumentation of the airway with an endotracheal tube (ETT), followed by microaspiration of contaminated secretions. VAP prevention will probably be most effective via a multifaceted approach, which includes meticulous attention to basic infection-control methods during patient care, proper patient positioning, oral hygiene, and removal of the ETT as soon as indicated. Modification of the ETT to reduce microaspiration and/or biofilm formation may also play an important role in VAP prevention. However, despite numerous studies of various such interventions, there is insufficient evidence upon which to base strong recommendations, and important safety concerns remain regarding the use of some devices. Most importantly, cost-effectiveness data are lacking for modified ETTs designed to prevent VAP. It is critical that future studies of ETTs designed to prevent VAP be adequately powered to demonstrate efficacy on important patient outcomes and safety, in addition to cost-effectiveness.

Randomized trial of light versus deep sedation on mental health after critical illness.

OBJECTIVES: : To investigate if light sedation favorably affects subsequent patient mental health compared with deep sedation. Symptoms of posttraumatic stress disorder are common in patients after they have undergone prolonged mechanical ventilation and are associated with sedation depth. DESIGN: : Randomized, open-label, controlled trial. SETTING: : Single tertiary care center. PATIENTS: : Adult patients requiring mechanical ventilation. INTERVENTIONS: : Patients were randomized to receive either light (patient awake and cooperative) or deep sedation (patient asleep, awakening upon physical stimulation). MEASUREMENTS AND MAIN RESULTS: : Self-reported measures of posttraumatic stress disorder, anxiety, and depression were collected at intensive care unit discharge and 4 wks later. The primary outcomes were symptoms of posttraumatic stress disorder, anxiety, and depression 4 wks after intensive care unit discharge.A total of 137 patients were assigned to either the light (n = 69) or the deep sedation (n = 68) group. Seven patients withdrew consent and one patient was randomized in error, leaving 129 patients (n = 65 in light sedation and n = 64 in deep sedation) available for analysis. At the 4-wk follow-up, patients in the deep sedation group tended to have more posttraumatic stress disorder symptoms (p = .07); the deep sedation group had more trouble remembering the event (37% vs. 14%; p = .02) and more disturbing memories of the intensive care unit (18% vs. 4%; p = .05). Patients in the light sedation group had an average one day less being ventilated and 1.5 fewer days in the intensive care unit. There were no differences between the two groups in the occurrence of anxiety and depression, and also no difference in mortality or in the incidence of adverse events. CONCLUSIONS: : These data suggest that a strategy of light sedation affords benefits with regard to reduction of intensive care unit stay and duration of ventilation without negatively affecting subsequent patient mental health or patient safety.

Active surface cooling protocol to induce mild therapeutic hypothermia after out-of-hospital cardiac arrest: a retrospective before-and-after comparison in a single hospital.

OBJECTIVE: To evaluate whether implementation of a therapeutic hypothermia protocol on arrival in a community hospital improved survival and neurologic outcomes in patients initially found to have ventricular fibrillation, pulseless electrical activity, or asystole, and then successfully resuscitated from out-of-hospital cardiac arrest. DESIGN: A retrospective study of patients who presented after implementation of a therapeutic hypothermia protocol compared with those who presented before the protocol was implemented. SETTING: Harborview Medical Center, Seattle, WA. PATIENTS: A total of 491 consecutive adults with out-of-hospital, nontraumatic cardiac arrest who presented between January 1, 2000 and December 31, 2004. INTERVENTIONS: An active cooling therapeutic hypothermia protocol, using ice packs, cooling blankets, or cooling pads to achieve a temperature of 32 degrees C to 34 degrees C was initiated on November 18, 2002 for unconscious patients resuscitated from cardiac arrest. MEASUREMENTS AND MAIN RESULTS: Demographics and outcomes were obtained from medical records and an emergency medical database. The primary outcomes were survival and favorable neurologic outcome at discharge associated with the therapeutic hypothermia protocol. An adjusted analysis was performed, using a multivariate regression. During the therapeutic hypothermia period, 204 patients were brought to the emergency department; of these 204 patients, 132 (65%) ultimately achieved temperatures of <34 degrees C. Of the 72 patients who did not achieve goal temperatures: 40 (20%) died in the emergency department or shortly after being admitted to the hospital, 15 (7%) regained consciousness, four (2%) had contraindications, 13 (6%) had temperature increase or did not have documented use of the therapeutic hypothermia protocol. In the prior period, none of the 287 patients received active cooling. Patients admitted in the therapeutic hypothermia period had a mean esophageal temperature of 34.1 degrees C during the first 12 hrs compared with 35.2 degrees C in the pretherapeutic hypothermia period (p < .01). Survival to hospital discharge improved in the therapeutic hypothermia period in patients with an initial rhythm of ventricular fibrillation (odds ratio, 1.88, 95% confidence interval, 1.03-3.45), however not in patients with nonventricular fibrillation (odds ratio, 1.17, 95% confidence interval, 0.66-2.05). In adjusted analysis, ventricular fibrillation patients during the therapeutic hypothermia period trended toward improved survival (odds ratio, 1.71, 95% confidence interval, 0.85-3.46) and had favorable neurologic outcome (odds ratio, 2.62, 95% confidence interval, 1.1-6.27) compared with the earlier period. This benefit was not observed in patients whose initial rhythm was pulseless electrical activity or asystole. CONCLUSIONS: The therapeutic hypothermia period was associated with a significant improvement in neurologic outcomes in patients whose initial rhythm was ventricular fibrillation, but not in patients with other rhythms.

Which H is the most important in triple-H therapy for cerebral vasospasm?

PURPOSE OF REVIEW: To summarize the recent literature of the hemodynamic management of subarachnoid hemorrhage and cerebral vasospasm, also designated as 'triple-H' therapy, and discuss each component of this management approach individually. RECENT FINDINGS: Following the publication of a review on circulatory volume expansion in the Cochrane Registry database in 2004 and a meta-analysis in 2003, there are no new randomized trials of triple-H therapy to prevent or treat cerebral vasospasm. However, physiological studies have been reported that contribute to the understanding of some of the components of triple-H therapy. SUMMARY: There remains a paucity of information regarding the efficacy and safety of triple-H therapy. The complexity in exploring this topic derives not only from the interdependence of the different components of triple-H therapy but also by the limitation in the assessment of hemodynamic variables. However, there is some emerging physiologic data suggesting that normovolemic hypertension may be the component most likely to increase cerebral blood flow after subarachnoid hemorrhage. In contrast, hypervolemic hemodilution is associated with increased complications and might also lower the hemoglobin to excessively low levels.

Pilot randomized clinical trial of prehospital induction of mild hypothermia in out-of-hospital cardiac arrest patients with a rapid infusion of 4 degrees C normal saline.

BACKGROUND: Although delayed hospital cooling has been demonstrated to improve outcome after cardiac arrest, in-field cooling started immediately after the return of spontaneous circulation may be more beneficial. The aims of the present pilot study were to assess the feasibility, safety, and effectiveness of in-field cooling. METHODS AND RESULTS: We determined the effect on esophageal temperature, before hospital arrival, of infusing up to 2 L of 4 degrees C normal saline as soon as possible after resuscitation from out-of-hospital cardiac arrest. A total of 125 such patients were randomized to receive standard care with or without intravenous cooling. Of the 63 patients randomized to cooling, 49 (78%) received an infusion of 500 to 2000 mL of 4 degrees C normal saline before hospital arrival. These 63 patients experienced a mean temperature decrease of 1.24+/-1 degrees C with a hospital arrival temperature of 34.7 degrees C, whereas the 62 patients not randomized to cooling experienced a mean temperature increase of 0.10+/-0.94 degrees C (P<0.0001) with a hospital arrival temperature of 35.7 degrees C. In-field cooling was not associated with adverse consequences in terms of blood pressure, heart rate, arterial oxygenation, evidence for pulmonary edema on initial chest x-ray, or rearrest. Secondary end points of awakening and discharged alive from hospital trended toward improvement in ventricular fibrillation patients randomized to in-field cooling. CONCLUSIONS: These pilot data suggest that infusion of up to 2 L of 4 degrees C normal saline in the field is feasible, safe, and effective in lowering temperature. We propose that the effect of this cooling method on neurological outcome after cardiac arrest be studied in larger numbers of patients, especially those whose initial rhythm is ventricular fibrillation.

Effects of anemia and hypotension on porcine optic nerve blood flow and oxygen delivery.

BACKGROUND: Perioperative ischemic optic neuropathy occurs after major surgical procedures, which are often associated with hypotension, anemia, or venous congestion. However, the effects of these conditions on optic nerve (ON) blood flow are unknown and cannot be studied adequately in humans. METHODS: Farm-raised pigs were anesthetized with isoflurane, kept normocapnic and normothermic, and subjected to conditions of euvolemic or hypovolemic hypotension (mean arterial pressure 50-55 mm Hg), anemia (hematocrit 17%), venous congestion, and combinations thereof. Control animals were kept euvolemic and normotensive for the entire experiment. Fluorescent microspheres were used to measure cerebral blood flow (CBF) and ON blood flow at baseline and after experimental conditions, and to calculate oxygen delivery (DO2). RESULTS: No significant changes in CBF or ON blood flow or DO2 occurred with euvolemic hypotension (n = 5), compared with controls (n = 12). Hypovolemic hypotension (n = 4) resulted in stable CBF and cerebral DO2, but significant reductions in ON DO2 (P = 0.032). The significant increase in CBF associated with anemia (n = 6) resulted in stable cerebral DO2. In contrast, ON blood flow did not significantly change with anemia, with (n = 5) or without (n = 6) euvolemic hypotension, resulting in significant reductions in ON DO2 (P < 0.01). CONCLUSION: Compensatory mechanisms for porcine CBF maintain stable DO2 under specified conditions of hypotension or anemia, whereas ON compensatory mechanisms were unable to maintain blood flow and to preserve DO2. The authors conclude that the porcine ON is more susceptible to physiologic perturbations than the brain.

Intensive insulin therapy and mortality in critically ill patients.

INTRODUCTION: Intensive insulin therapy (IIT) with tight glycemic control may reduce mortality and morbidity in critically ill patients and has been widely adopted in practice throughout the world. However, there is only one randomized controlled trial showing unequivocal benefit to this approach and that study population was dominated by post-cardiac surgery patients. We aimed to determine the association between IIT and mortality in a mixed population of critically ill patients. METHODS: We conducted a cohort study comparing three consecutive time periods before and after IIT protocol implementation in a Level 1 trauma center: period I (no protocol); period II, target glucose 80 to 130 mg/dL; and period III, target glucose 80 to 110 mg/dL. Subjects were 10,456 patients admitted to intensive care units (ICUs) between 1 March 2001 and 28 February 2005. The main study endpoints were ICU and hospital mortality, Sequential Organ Failure Assessment score, and occurrence of hypoglycemia. Multivariable regression analysis was used to evaluate mortality and organ dysfunction during periods II and III relative to period I. RESULTS: Insulin administration increased over time (9% period I, 25% period II, and 42% period III). Nonetheless, patients in period III had a tendency toward higher adjusted hospital mortality (odds ratio [OR] 1.15, 95% confidence interval [CI] 0.98, 1.35) than patients in period I. Excess hospital mortality in period III was present primarily in patients with an ICU length of stay of 3 days or less (OR 1.47, 95% CI 1.11, 1.93 There was an approximately fourfold increase in the incidence of hypoglycemia from periods I to III. CONCLUSION: A policy of IIT in a group of ICUs from a single institution was not associated with a decrease in hospital mortality. These results, combined with the findings from several recent randomized trials, suggest that further study is needed prior to widespread implementation of IIT in critically ill patients.

Respiratory controversies in the critical care setting. Should weaning protocols be used with all patients who receive mechanical ventilation?

Ventilator weaning protocols have the potential to expedite the weaning process and have been shown to reduce weaning time and the duration of mechanical ventilation in several studies. However, other studies have found no benefits from weaning protocols, and they may be particularly superfluous in highly staffed and structured intensive care units. Furthermore, for a protocol to improve outcomes, the clinicians must have a high rate of adherence to the protocol. Weaning protocols might improve patient care and outcomes, but their implementation should be based on local clinical characteristics and needs, and accompanied by an intensive education effort and measurement of adherence and outcomes.

Respiratory controversies in the critical care setting. Should all patients be treated with hypothermia following cardiac arrest?

Cardiac arrest is a common and lethal medical problem; each year more than half a million people in the United States and Canada suffer cardiac arrest treated by emergency medical personnel or in-hospital providers. Of those who survive to hospital admission or suffer in-hospital arrest, 40-60% die prior to discharge. Neurologic injury is the major source of morbidity and mortality after recovery of spontaneous circulation. Therapeutic options to prevent neurologic injury are limited, but recent randomized trials showed that moderate therapeutic hypothermia improves neurologic outcome in selected patients following cardiac arrest. Clear consensus statements recommend that unconscious adult patients with spontaneous circulation after out-of-hospital cardiac arrest should be cooled if the initial rhythm was ventricular fibrillation, and that therapeutic hypothermia should be considered for other patients (other rhythms or in-hospital arrest). However, the position that all patients should be cooled following cardiac arrest is probably too broad, given the lack of studies on patients with non-ventricular-fibrillation rhythms, in-hospital arrest, or non-cardiac causes of arrest. Further research is needed to determine the broadest application of moderate therapeutic hypothermia.

Pilot study of rapid infusion of 2 L of 4 degrees C normal saline for induction of mild hypothermia in hospitalized, comatose survivors of out-of-hospital cardiac arrest.

BACKGROUND: Recent clinical studies have demonstrated that mild hypothermia (32 degrees C to 34 degrees C) induced by surface cooling improves neurological outcome after resuscitation from out-of-hospital cardiac arrest. Results from animal models suggest that the effectiveness of mild hypothermia could be improved if initiated as soon as possible after return of spontaneous circulation. Infusion of cold, intravenous fluid has been proposed as a safe, effective, and inexpensive technique to induce mild hypothermia after cardiac arrest. METHODS AND RESULTS: In 17 hospitalized survivors of out-of-hospital cardiac arrest, we determined the effect on temperature and hemodynamics of infusing 2 L of 4 degrees C cold, normal saline during 20 to 30 minutes into a peripheral vein with a high-pressure bag. Data on vital signs, electrolytes, arterial blood gases, and coagulation were collected before and after fluid infusion. Cardiac function was assessed by transthoracic echocardiography before fluid administration and 1 hour after infusion. Passive (fans, leaving patient uncovered) or active (cooling blankets, neuromuscular blockade) cooling measures were used to maintain mild hypothermia for 24 hours. Infusion of 2 L of 4 degrees C cold, normal saline resulted in a mean temperature drop of 1.4 degrees C 30 minutes after the initiation of infusion. Rapid infusion of fluid was not associated with clinically important changes in vital signs, electrolytes, arterial blood gases, or coagulation parameters. The initial mean ejection fraction was 34%, and fluid infusion did not affect ejection fraction or increase central venous pressure, pulmonary pressures, or left atrial filling pressures as assessed by echocardiography. Passive measures were ineffective in maintaining hypothermia compared with active measures. CONCLUSIONS: Infusion of 2 L of 4 degrees C cold, normal saline is safe and effective in rapidly lowering body temperature in survivors of out-of-hospital cardiac arrest.