Search

Background: Cerebrospinal fluid creatine kinase BB isoenzyme (CSF CK-BB) after cardiac arrest (CA) has been shown to have a high positive predictive value for poor neurological outcome, but it has not been evaluated in the setting of targeted temperature management (TTM) and modern CA care. We aimed to evaluate CSF CK-BB as a prognostic biomarker after CA. Methods: We performed a retrospective cohort study of patients with CA admitted between 2010 and 2020 to a three-hospital health system who remained comatose and had CSF CK-BB assayed between 36 and 84 h after CA. We examined the proportion of patients at hospital discharge who achieved favorable or intermediate neurological outcome, defined as Cerebral Performance Category score of 1–3, compared with those with poor outcome (Cerebral Performance Category score 4–5) for various CSF CK-BB thresholds. We also evaluated additive value of bilateral absence of somatosensory evoked potentials (SSEPs). Results: Among 214 eligible patients, the mean age was 54.7 ± 4.8 years, 72% of patients were male, 33% were nonwhite, 17% had shockable rhythm, 90% were out-of-hospital CA, and 83% received TTM. A total of 19 (9%) awakened. CSF CK-BB ≥ 230 U/L predicted a poor outcome at hospital discharge, with a specificity of 100% (95% confidence interval [CI] 82–100%) and sensitivity of 69% (95% CI 62–76%). When combined with bilaterally absent N20 response on SSEP, specificity remained 100% while sensitivity increased to 80% (95% CI 73–85%). Discordant CK-BB and SSEP findings were seen in 13 (9%) patients. Conclusions: Cerebrospinal fluid creatine kinase BB isoenzyme levels accurately predicted poor neurological outcome among CA survivors treated with TTM. The CSF CK-BB cutoff of 230 U/L optimizes sensitivity to 69% while maintaining a specificity of 100%. CSF CK-BB could be a useful addition to multimodal neurological prognostication after CA. [ABSTRACT FROM AUTHOR]

Background: The main focus of traumatic brain injury (TBI) management is prevention of secondary injury. Therapeutic hypothermia (TH), the induction of a targeted low core body temperature, has been explored as a potential neuroprotectant in TBI. The aim of this article is to synthesize the available clinical data comparing the use of TH with the use of normothermia in TBI. Methods: A systematic search was conducted through MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials for randomized clinical trials including one or more outcome of interest associated with TH use in TBI. Independent reviewers evaluated quality of the studies and extracted data on patients with TBI undergoing TH treatment compared with those undergoing normothermia treatment. Pooled estimates, confidence intervals (CIs), and risk ratios (RRs) or odds ratios were calculated for all outcomes. Results: A total of 3,909 patients from 32 studies were eligible for analysis. Pooled analysis revealed a significant benefit of TH on mortality and functional outcome (RR 0.81, 95% CI 0.68–0.96, I2 = 41%; and RR 0.77; 95% CI 0.67–0.88, I2 = 68%, respectively). However, subgroup analysis based on risk of bias showed that only studies with a high risk of bias maintained this benefit. When divided by cooling method, reduced poor functional outcome was seen in the systemic surface cooling and cranial cooling groups (RR 0.68, 95% CI 0.59–0.79, I2 = 35%; and RR 0.44, 95% CI 0.29–0.67, I2 = 0%), and no difference was seen for the systemic intravenous or gastric cooling group. Reduced mortality was only seen in the systemic surface cooling group (RR 0.63, 95% CI 0.53–0.75, I2 = 0%,); however, this group had mostly high risk of bias studies. TH had an increased rate of pneumonia (RR 1.24, 95% CI 1.10–1.40, I2 = 32%), coagulation abnormalities (RR 1.63, 95% CI 1.09–2.44, I2 = 55%), and cardiac arrhythmias (RR 1.78, 95% CI 1.05–3.01, I2 = 21%). Once separated by low and high risk of bias, we saw no difference in these complications in the groups with low risk of bias. Overall quality of the evidence was moderate for mortality, functional outcome, and pneumonia and was low for coagulation abnormalities and cardiac arrhythmias. Conclusions: With the addition of several recent randomized clinical trials and a thorough quality assessment, we have provided an updated systematic review and meta-analysis that concludes that TH does not show any benefit over normothermia in terms of mortality and functional outcome. [ABSTRACT FROM AUTHOR]

This article discusses the use of therapeutic hypothermia (TH) in the treatment of traumatic brain injury (TBI). While TH has been used for centuries and is thought to modulate key mechanisms involved in secondary brain injury, recent clinical studies have shown mixed results. Some studies have shown associations between TH and improved outcomes, while others have not. Meta-analyses have also produced conflicting results. The authors of this article conducted a large meta-analysis and found that TH was associated with a reduction in mortality and poor neurologic outcomes, but also an increased risk of complications. However, the results were limited by methodological concerns and heterogeneity in the data. The authors suggest that further research is needed to refine cooling methods, identify subpopulations that may benefit from TH, and explore the use of TH in combination with other neuroprotective strategies. [Extracted from the article]

Background: The objective of this study is to describe incidence and factors associated with early withdrawal of life-sustaining therapies based on presumed poor neurologic prognosis (WLST-N) and practices around multimodal prognostication after out-of-hospital cardiac arrest (OHCA). Methods: We performed a subanalysis of a randomized controlled trial assessing prehospital therapeutic hypothermia in adult patients admitted to nine hospitals in King County with nontraumatic OHCA between 2007 and 2012. Patients who underwent tracheal intubation and were unconscious following return of spontaneous circulation were included. Our outcomes were (1) incidence of early WLST-N (WLST-N within < 72 h from return of spontaneous circulation), (2) factors associated with early WLST-N compared with patients who remained comatose at 72 h without WLST-N, (3) institutional variation in early WLST-N, (4) use of multimodal prognostication, and (5) use of sedative medications in patients with early WLST-N. Analysis included descriptive statistics and multivariable logistic regression. Results: We included 1,040 patients (mean age was 65 years, 37% were female, 41% were White, and 44% presented with arrest due to ventricular fibrillation) admitted to nine hospitals. Early WLST-N accounted for 24% (n = 154) of patient deaths and occurred in half (51%) of patients with WLST-N. Factors associated with early WLST-N in multivariate regressions were older age (odds ratio [OR] 1.02, 95% confidence interval [CI]: 1.01–1.03), preexisting do-not-attempt-resuscitation orders (OR 4.67, 95% CI: 1.55–14.01), bilateral absent pupillary reflexes (OR 2.4, 95% CI: 1.42–4.10), and lack of neurological consultation (OR 2.60, 95% CI: 1.52–4.46). The proportion of patients with early WLST-N among all OHCA admissions ranged from 19–60% between institutions. A head computed tomography scan was obtained in 54% (n = 84) of patients with early WLST-N; 22% (n = 34) and 5% (n = 8) underwent ≥ 1 and ≥ 2 additional prognostic tests, respectively. Prognostic tests were more frequently performed when neurological consultation occurred. Most patients received sedating medications (90%) within 24 h before early WLST-N; the median time from last sedation to early WLST-N was 4.2 h (interquartile range 0.4–15). Conclusions: Nearly one quarter of deaths after OHCA were due to early WLST-N. The presence of concerning neurological examination findings appeared to impact early WLST-N decisions, even though these are not fully reliable in this time frame. Lack of neurological consultation was associated with early WLST-N and resulted in underuse of guideline-concordant multimodal prognostication. Sedating medications were often coadministered prior to early WLST-N and may have further confounded the neurological examination. Standardizing prognostication, restricting early WLST-N, and a multidisciplinary approach including neurological consultation might improve outcomes after OHCA. [ABSTRACT FROM AUTHOR]

Background: Endoplasmic reticulum stress (ERS) plays a vital role in mediating apoptosis in the brain following cardiac arrest (CA). Studies have shown that therapeutic hypothermia (TH) provides neuroprotection through anti-apoptosis; however, the effects of temperature variability in TH on the brain remain unclear. In this study, we investigated the different effects of temperature variability through extracorporeal membrane oxygenation on apoptosis and ERS in the brain following CA. Methods: Eighteen male domestic pigs underwent 6-min duration of no-flow induced by ventricular fibrillation. Extracorporeal cardiopulmonary resuscitation was then performed, and the return of spontaneous circulation (ROSC) was achieved. The animals were randomly assigned to the following groups: normothermia, non-temperature variability, and temperature variability. TH (core temperature, 33–35 °C) was maintained for 24 h post-ROSC, and the animals were rewarmed for 8 h. Quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry for Bax and Bcl-2 transcripts and proteins, respectively, were used to investigate apoptosis in the cerebral cortex. Expression levels of the ERS molecules, GRP78 and CHOP, were also detected by qRT-PCR, and cellular morphology was evaluated using transmission electron microscopy. Results: qRT-PCR and immunohistochemistry results revealed that TH significantly increased the expression levels of Bcl-2 and GRP78 and decreased that of Bax and CHOP than under normothermia conditions. Compared to the non-temperature variability group, temperature variability did not decrease the expression levels of Bcl-2 and GRP78 and not increase the levels of Bax and CHOP. Endoplasmic reticulum ultrastructural changes were significantly improved under TH. No statistical difference was observed between the temperature variability and non-temperature variability groups. Conclusion: TH can reduce neuronal apoptosis by ERS, while temperature variability does not attenuate this beneficial effect. [ABSTRACT FROM AUTHOR]

Background: Controversy surrounds utilization of induced hypothermia (IHT) in comatose cardiac arrest (CA) survivors with a non-shockable rhythm. Methods: We conducted a meta-analysis and trial sequential analysis (TSA) comparing IHT with no IHT approaches in patients with CA and a non-shockable rhythm. The primary outcome of interest was favorable neurological outcomes (FNO) defined using the Cerebral Performance Category (CPC) score of 1 or 2. Secondary endpoints were survival at discharge and survival beyond 90 days. Results: A total of 9 studies with 10,386 patients were included. There was no difference between both groups in terms of FNO (13% vs. 13%, RR 1.34, 95% CI 0.96–1.89, p = 0.09, I2 = 88%), survival at discharge (20% vs. 22%, RR 1.09, 95% CI 0.88–1.36, p = 0.42, I2 = 76%), or survival beyond 90 days (16% vs. 15%, RR 0.92, 95% CI 0.61–1.40, p = 0.69, I2 = 83%). The TSA showed firm evidence supporting the lack of benefit of IHT in terms of survival at discharge. However, the Z-curves failed to cross the conventional and TSA (futility) boundaries for FNO and survival beyond 90 days, indicating lack of sufficient evidence to draw firm conclusions regarding these outcomes. Conclusion: In this meta-analysis of 9 studies, the utilization of IHT was not associated with a survival benefit at discharge. Although the meta-analysis showed lack of benefit of IHT in terms of FNO and survivals beyond 90 days, the corresponding TSA showed high probability of type-II statistical error, and therefore more randomized controlled trials powered for these outcomes are needed. [ABSTRACT FROM AUTHOR]

Background: Acute brain lesions constitute an alarming public health concern. Neuroprotective therapies have been implemented to stabilize, prevent, or reduce brain lesions, thus improving neurological outcomes and survival rates. Hypothermia is the most effective approach, mainly attributed to the reduction in cellular metabolic activity. Whole-body cooling is currently implemented by healthcare professionals; however, adverse events are frequent, limiting the potential benefits of therapeutic hypothermia. Therefore, selective methods have been developed to reduce adverse events while delivering neuroprotection. Nasopharyngeal approaches are the safest and most effective methods currently considered. Our primary objective was to determine the effects of a novel nasopharyngeal catheter on the brain temperature of pigs.Methods: In this prospective, non-randomized, interventional experimental trial, 10 crossbred pigs underwent nasopharyngeal cooling for 60 min followed by 15 min of rewarming. Nasopharyngeal catheters were inserted into the left nostril and properly positioned at the nasopharyngeal cavity.Results: Nasopharyngeal cooling was associated with a decrease in brain temperature, which was more significant in the left cerebral hemisphere (p = 0.01). There was a reduction of 1.47 ± 0.86 °C in the first 5 min (p < 0.001), 2.45 ± 1.03 °C within 10 min (p < 0.001), and 4.45 ± 1.36 °C after 1 h (p < 0.001). The brain-core gradient was 4.57 ± 0.87 °C (p < 0.001). Rectal, esophageal, and pulmonary artery temperatures and brain and systemic hemodynamic parameters, remained stable during the procedure. Following brain cooling, values of oxygen partial pressure in brain tissue significantly decreased. No mucosal lesions were detected during nasal, pharyngeal, or oral inspection after nasopharyngeal catheter removal.Conclusions: In this study, a novel nasopharyngeal cooling catheter effectively induced and maintained exclusive brain cooling when combined with effective counter-warming methods. Exclusive brain cooling was safe with no device-related local or systemic complications and may be desired in selected patient populations. [ABSTRACT FROM AUTHOR]

Background: Glucose control status after cardiac arrest depending on chronic glycemic status and the association between chronic glycemic status and outcome in cardiac arrest survivors are not well known. We investigated the association between glycated hemoglobin (HbA1c) and 6-month neurologic outcome in cardiac arrest survivors undergoing therapeutic hypothermia (TH) and whether mean glucose, area under curve (AUC) of glucose during TH, and neuron-specific enolase (NSE) are different between normal and high HbA1c groups.Methods: This retrospective single-center study included adult comatose cardiac arrest survivors who underwent TH from September 2011 to December 2017. HbA1c and glucose were measured after return of spontaneous circulation (ROSC), and normal or high HbA1c was defined using cutoff value of 6.4% of HbA1c. Blood glucose was measured at least every 4 h and treated with a written protocol to maintain the range of 80-200 mg/dL. Hypoglycemia and hyperglycemia were defined with glucose < 70 or > 180 mg/dL. Mean glucose during induction and rewarming phase and AUC of glucose during every 6 h of maintenance were calculated, and NSE at 48 h after cardiac arrest was recorded. The primary outcome was unfavorable neurologic outcome, defined as Glasgow Pittsburgh Cerebral Performance Category scale 3-5 at 6 months after cardiac arrest.Results: Of 384 included patients, 81 (21.1%) had high HbA1c and 247 (64.3%) had an unfavorable neurologic outcome. Patients with high HbA1c were more common in the unfavorable group than in favorable group (27.5% vs 9.5%, p < 0.001), and the unfavorable group had significantly higher HbA1c level (5.8% [5.4-6.8%] vs 5.6% [5.3-6.0%], p = 0.007). HbA1c level was independently associated with worse neurologic outcome (odds ratio 1.414; 95% confidence interval 1.051-1.903). High HbA1c group had higher glucose after ROSC, glucose AUC during maintenance, and rewarming phase than normal HbA1c group. High HbA1c group had significantly higher incidence of hyperglycemia throughout the TH, while normal HbA1c group had significantly higher incidence of normoglycemia. However, no glucose parameter remained as an independent predictor of neurologic outcome after adjustment, irrespective of HbA1c level. NSE showed good prognostic performance (area under curve 0.892; cutoff value 26.3 ng/mL). Although NSE level was not different between HbA1c groups, high HbA1c group had higher proportion of patient having NSE over cutoff.Conclusions: Higher HbA1c was independently associated with unfavorable neurologic outcome. Glycemic status during TH was different between normal and high HbA1c groups. [ABSTRACT FROM AUTHOR]

Background: The absence of the pupillary light reflex (PLR) 3 days after cardiac arrest predicts poor outcome, but quantitative PLR assessment with pupillometry early after recovery of spontaneous circulation (ROSC) and throughout targeted temperature management (TTM) has rarely been evaluated.Methods: Fifty-five adult patients treated with TTM with available pupillometry data from the NeurOptics NPi-200 were studied. Discharge outcome was classified good if the cerebral performance category score was 1-2, poor if 3-5. Pupil size, PLR percent constriction (%PLR), and constriction velocity (CV) were determined at TTM start and 6 (± 2)-h post-ROSC ("early"), and throughout TTM using data from the worst eye at each assessment. The Neurological Pupil index (NPi) was also determined at each pupil assessment; the NPi is scored from 0 (nonreactive) to 5 (brisk) with values < 3 considered sluggish or abnormal. Prognostic performance to predict poor outcome was assessed with receiver operator characteristic curves.Results: All nine patients with ≥ 1 nonreactive pupil (NPi = 0) within 6 (± 2) h after ROSC died, and 12/14 (86%) with sluggish pupils (0 < NPi < 3) had poor outcomes. 15/29 (52%) patients with normal pupil reactivity (NPi ≥ 3) had poor outcomes, four survived with cerebral performance category = 3, three died of cardiac causes, and eight died of neurologic causes. During TTM, 20/21 (95%) patients with nonreactive pupils had poor outcomes, 9/14 (64%) of patients with sluggish pupils had poor outcomes, and 9/20 (45%) with normal pupil reactivity had poor outcomes. Pupil size did not predict outcome, but NPi (AUC = 0.72 [0.59-0.86], p < 0.001), %PLR (AUC = 0.75 [0.62-0.88], p < 0.001) and CV (AUC = 0.78 [0.66-0.91], p < 0.001) at 6 h predicted poor outcome. When nonreactive pupils were first detected, 75% were < 5 mm.Conclusions: Very early after resuscitation from cardiac arrest, abnormal Neurological Pupil index and pupillary light reflex measurements by pupillometer are predictive of poor outcome, and are not usually associated with dilated pupils. [ABSTRACT FROM AUTHOR]

Background/objective: The outcomes of patients with non-shockable out-of-hospital cardiac arrest (non-shockable OHCA) are poorer than those of patients with shockable out-of-hospital cardiac arrest (shockable OHCA). In this retrospective study, we selected patients from the SOS-KANTO 2012 study with non-shockable OHCA that developed after emergency medical service (EMS) arrival and analyzed the effect of therapeutic hypothermia (TH) on non-shockable OHCA patients.Methods: Of 16,452 patients who have definitive data on the 3-month outcome in the SOS-KANTO 2012 study, we selected 241 patients who met the following criteria: age ≥ 18 years, normal spontaneous respiration or palpable pulse upon emergency medical services arrival, no ventricular fibrillation or pulseless ventricular tachycardia before hospital arrival, and achievement of spontaneous circulation without cardiopulmonary bypass. Patients were divided into two groups based on the presence or absence of TH and were analyzed.Results: Of the 241 patients, 49 underwent TH. Univariate analysis showed that the 1-/3-month survival rates and favorable 3-month cerebral function outcome rates in the TH group were significantly better than the non-TH group (46% vs 19%, respectively, P < 0.001, 35% vs 12%, respectively, P < 0.001, 20% vs 7%, respectively, P = 0.01). Multivariate logistic regression analysis showed that TH was a significant, independent prognostic factor for cerebral function outcome.Conclusions: In this study, TH was an independent prognostic factor for the 3-month cerebral function outcome. Even in patients with non-shockable OHCA, TH may improve outcome if the interval from the onset of cardiopulmonary arrest is relatively short, and adequate cardiopulmonary resuscitation is initiated immediately after onset. [ABSTRACT FROM AUTHOR]

Background: Cerebral edema is one of the major causes of mortality following cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). A subunit of the sulfonylurea receptor 1-transient receptor potential M4 (Sur1-TRPM4) channel has been implicated in the pathogenesis of ischemia-evoked cerebral edema. In this study, we examined whether glibenclamide (GBC), a Sur1-TRPM4 channel inhibitor, attenuates cerebral edema following CA/CPR and further examined the efficacy of GBC combined with therapeutic hypothermia.Methods: Isoflurane-anesthetized adult male wild-type C57Bl/6 mice subjected to 7-min CA/CPR were randomized into five groups: sham operation, control with normothermia, GBC with normothermia, control with hypothermia, and GBC with hypothermia. The primary outcome was to evaluate regional brain water content; the secondary outcome was to measure blood glucose level, Sur1-TRPM4 expression, and pro-inflammatory factor expression.Results: Compared with normothermia, GBC treatment or hypothermia significantly attenuated brain water content in mice subjected to CA/CPR. GBC combined with hypothermia had no additional effects on attenuating cerebral edema. Pro-inflammatory factor messenger RNA expression (TNF-α and IL-6), NFκβ activation, and SUR1-TRPM4 levels were upregulated after CA/CPR. Compared with normothermia, hypothermia, but not GBC, partly suppressed these factors' expression.Conclusions: GBC attenuated cerebral edema following CA/CPR by blocking Sur1-TRPM4 channels upregulated by CA insult. The effect of GBC was comparable with that of therapeutic hypothermia alone. These results suggest that GBC is an alternative approach for treating CA-evoked cerebral edema. [ABSTRACT FROM AUTHOR]

Background: Targeted temperature management (TTM) is often used in neurocritical care to minimize secondary neurologic injury and improve outcomes. TTM encompasses therapeutic hypothermia, controlled normothermia, and treatment of fever. TTM is best supported by evidence from neonatal hypoxic-ischemic encephalopathy and out-of-hospital cardiac arrest, although it has also been explored in ischemic stroke, traumatic brain injury, and intracranial hemorrhage patients. Critical care clinicians using TTM must select appropriate cooling techniques, provide a reasonable rate of cooling, manage shivering, and ensure adequate patient monitoring among other challenges.Methods: The Neurocritical Care Society recruited experts in neurocritical care, nursing, and pharmacotherapy to form a writing Committee in 2015. The group generated a set of 16 clinical questions relevant to TTM using the PICO format. With the assistance of a research librarian, the Committee undertook a comprehensive literature search with no back date through November 2016 with additional references up to March 2017.Results: The Committee utilized GRADE methodology to adjudicate the quality of evidence as high, moderate, low, or very low based on their confidence that the estimate of effect approximated the true effect. They generated recommendations regarding the implementation of TTM based on this systematic review only after considering the quality of evidence, relative risks and benefits, patient values and preferences, and resource allocation.Conclusion: This guideline is intended for neurocritical care clinicians who have chosen to use TTM in patient care; it is not meant to provide guidance regarding the clinical indications for TTM itself. While there are areas of TTM practice where clear evidence guides strong recommendations, many of the recommendations are conditional, and must be contextualized to individual patient and system needs. [ABSTRACT FROM AUTHOR]

Background: Targeted temperature management (TTM) confers neurological and survival benefits for post-cardiac arrest patients with return of spontaneous circulation (ROSC) who remain comatose. Specialized equipment for induction of hypothermia is not available in the prehospital setting, and there are no reliable methods for emergency medical services personnel to initiate TTM. We hypothesized that the application of surface cooling elements to the neck will decrease brain temperature and act as initiators of TTM.Methods: Magnetic resonance (MR) spectroscopy was used to evaluate the effect of a carotid surface cooling element on brain temperature in healthy adults.Results: Six individuals completed this study. We measured a temperature drop of 0.69 ± 0.38 °C (95% CI) in the cortex of the brain following the application of the cooling element. Application of a room temperature element also caused a measurable decrease in brain temperature of 0.66 ± 0.41 °C (95% CI) which may be attributable to baroreceptor activation.Conclusion: The application of surface cooling elements to the neck decreased brain temperature and may serve as a method to initiate TTM in the prehospital setting. [ABSTRACT FROM AUTHOR]

Background: Hyperglycemia in out-of-hospital cardiac arrest (OHCA) survivors is associated with poor outcomes. However, in the control of initial hyperglycemia, an adequate strategy to improve patients' neurologic outcomes remains undetermined. Prior to the establishment of such strategy, we need to determine whether a decreased rate of initial blood glucose (BG) affects patient outcomes.Methods: One hundred and forty-five adult non-traumatic OHCA survivors treated with therapeutic hypothermia between April 2007 and December 2011 were enrolled in this single-center retrospective cohort study. Based on the cerebral performance category (CPC) at 6 months after OHCA, study populations were categorized as "Good CPC group" (favorable outcome, CPC1 and CPC2) and "Poor CPC group" (unfavorable outcome, CPC3-CPC5). Variables related to BG were obtained, and the rate of BG change was calculated.Results: In the Good CPC group, the time required to attain target BG levels was shorter [7.4 (2.97-18.13) vs. 13.17 (7.55-27.0) h, p < 0.001], and the average rate of glucose decrease until the attainment of target BG levels was faster [17.06 (6.67-34.49) vs. 8.33 (4.26-18.55) mg/dl/h, p = 0.005] than in the Poor CPC group. Using multivariate analysis, the faster rate (odds ratio 1.074; 95% confidence interval 1.029-1.12; p = 0.001) and the shorter time (odds ratio 13.888; 95% confidence interval 2.271-84.906; p = 0.004) required to attain target BG levels were independently related to favorable neurologic outcomes.Conclusions: Faster rates of initial BG decrease and the shorter time required to attain target BG levels were associated with favorable neurologic outcome in survivors of OHCA receiving therapeutic hypothermia. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate the prognostic value of continuous electroencephalogram (cEEG) during the first 48 h following cardiac arrest (CA) in patients treated with targeted temperature management (TTM).Methods: We reviewed data from 92 comatose post-CA patients over a 6 year-period; cEEG recordings were performed during TTM and restoration of normothermia. EEG findings were divided into four time-periods: 0-8, 8-16, 16-24, and 24-48 h after CA. Background EEG findings were defined as moderate encephalopathy (diffuse slowing with reactivity/variability), severe encephalopathy (diffuse slowing without reactivity/variability), burst suppression or suppression, and dichotomized as malignant (suppression/burst suppression/severe encephalopathy) or benign (moderate encephalopathy). Epileptiform activity was defined as the presence of seizures, sporadic epileptiform discharges, or periodic discharges. Neurological outcome was assessed at 3 months using the cerebral performance categories (CPC) score (good outcome: CPC 1-2).Results: 26/92 (28%) patients had a good outcome. Malignant patterns were associated with a poor outcome at all time-points, with a high positive predictive value (94-97%) but a poor negative predictive value (44-56%). Epileptiform activity did not influence the prognostic value of EEG patterns. All patients with moderate encephalopathy and seizures or generalized periodic discharges had a poor outcome.Conclusions: cEEG can identify patients with poor outcome from the first hours following CA, with limited predictive value for good outcome. Epileptiform activity did not improve the prognostic accuracy of EEG, but seizures and generalized periodic discharges were associated with poor outcome even when developing on a benign EEG pattern. [ABSTRACT FROM AUTHOR]

Objective: Therapeutic hypothermia (TH) improves neurologic outcome in patients resuscitated from ventricular fibrillation. The purpose of this study was to evaluate TH effects on neurologic outcome in patients resuscitated from a non-shockable out-of-hospital cardiac arrest rhythm.Design and Setting: This is a retrospective cohort study of data reported to a registry in an emergency medical system in a large metropolitan region. Patients achieving field return of spontaneous circulation are transported to designated hospitals with TH protocols.Patients: Patients with an initial non-shockable rhythm were identified. Patients were excluded if awake in the Emergency Department or if TH was withheld due to preexisting coma or death prior to initiation. The decision to initiate TH was determined by the treating physician.Measurements: The primary outcome was survival with good neurologic outcome defined by a cerebral performance category of 1 or 2.Main Results: Of the 2772 patients treated for cardiac arrest during the study period, there were 1713 patients resuscitated from cardiac arrest with an initial non-shockable rhythm and 1432 patients met inclusion criteria. The median age was 69 years [IQR 59-82]; 802 (56%) male. TH was induced in 596 (42%) patients. Survival with good neurologic outcome was 14% in the group receiving TH, compared with 5% in those not treated with TH (risk difference = 8%, 95% CI 5-12%). The adjusted OR for a CPC 1 or 2 with TH was 2.9 (95% CI 1.9-4.4).Conclusion: Analyzing the data collected from the registry of the standard practice in a large metropolitan region, TH is associated with improved neurologic outcome in patients resuscitated from initial non-shockable rhythms in a regionalized system for post-resuscitation care. [ABSTRACT FROM AUTHOR]

Background: Temperature management using endovascular catheters is an established therapy in neurointensive care. Nonetheless, several case series have reported a high rate of thrombosis related to the use of endovascular hypothermia catheters. Methods: As a result of a pulmonary embolism that developed in a patient after removing an inferior vena cava hypothermia catheter, we designed a clinical protocol for managing and removing these devices. First, an invasive cavography was performed before the removal of the catheter. If there was a thrombus, a cava vein filter was inserted through jugular access. After that, the catheter was removed. Results: The venography found inferior vena cava thrombi in 18 of 20 consecutive patients. A concomitant ultrasonography study showed vena cava thrombosis in only three patients. A vena cava filter was inserted in all patients where thrombi were found, without any significant complication. Anticoagulation was started in all patients. No symptomatic pulmonary embolism was diagnosed until the time of discharge. Conclusions: The frequency of thrombosis related to temperature management catheters is extremely high (90 %). Furthermore, ultrasonography has a very low sensibility to detect cava vein thrombosis (16.7 %). The real meaning of our findings is unknown, but other temperature control systems could be a safer option. More studies are needed to confirm our findings. [ABSTRACT FROM AUTHOR]

Background: Lack of electroencephalography (EEG) background reactivity during therapeutic hypothermia (TH) has been associated with poor outcome in post-anoxic comatose patients. However, decision on intensive care withdrawal is based on normothermic (NT) evaluations. This study aims at exploring whether patients showing recovery of EEG reactivity in NT after a non-reactive EEG in TH differ from those remaining non-reactive. Methods: Patients with non-reactive EEG during TH were identified from our prospective registry of consecutive comatose adults admitted after successful resuscitation from CA between April 2009 and June 2014. Variables including neurological examination, serum neuron-specific enolase (NSE), procalcitonin, and EEG features were compared regarding impact on functional outcome at 3 months. Results: Seventy-two of 197 patients (37 %) had a non-reactive EEG background during TH with thirteen (18 %) evolving towards reactivity in NT. Compared to those remaining non-reactive ( n = 59), they showed significantly better recovery of brainstem reflexes ( p < 0.001), better motor responses ( p < 0.001), transitory consciousness improvement ( p = 0.008), and a tendency toward lower NSE ( p = 0.067). One patient recovering EEG reactivity survived with good functional outcome at 3 months. Conclusions: Recovery of EEG reactivity from TH to NT seems to distinguish two patients' subgroups regarding early neurological assessment and transitory consciousness improvement, corroborating the role of EEG in providing information about cerebral functions. Understanding these dynamic changes encourages maintenance of intensive support in selected patients even after a non-reactive EEG background in TH, as a small subgroup may indeed recover with good functional outcome. [ABSTRACT FROM AUTHOR]

Background: Therapeutic strategies that cause an alteration in patient temperature, such as controlled normothermia (CN), therapeutic hypothermia (TH), and pentobarbital infusion (PI), are often used to manage complications caused by acute brain injury. The purpose of this study was to evaluate pharmacokinetic (PK) parameters of vancomycin in patients with acute brain injury undergoing temperature modulation. Methods: This was a retrospective cohort study of adult patients with acute brain injury admitted between May 2010 and March 2014 who underwent CN, TH, or PI and received vancomycin. Predicted PK parameters based on population data were compared with calculated PK parameters based on serum concentrations. Results: Seventeen CN patients and 10 TH/PI patients met inclusion criteria. Traumatic brain injury and aneurysmal subarachnoid hemorrhage accounted for the majority of admitting diagnoses. In the CN group, the median dose was 16.7 (15.5-18.4) mg/kg. The median calculated elimination rate constant [0.155 (0.108-0.17) vs. 0.103 (0.08-0.142) hr; p = 0.04] was significantly higher than the predicted value. The median measured trough concentration [8.9 (7.7-11.1) vs. 17.1 (10.8-22.3) υg/mL; p = 0.004] was significantly lower than predicted. In the TH/PI group, the median dose was 15.4 (14.7-17.2) mg/kg. No significant differences were found between the median calculated and predicted elimination rate constant [0.107 (0.097-0.109) vs. 0.112 (0.102-0.127) hr; p = 0.41] and median measured and predicted trough concentration [14.2 (12.7-17.1) vs. 13.1 (11-17.8) υg/mL; p = 0.71]. Conclusion: Patients who underwent TH/PI did not exhibit PK alterations when compared to predicted PK parameters based on population data, while patients who underwent CN experienced PK alterations favoring an increased elimination of vancomycin. [ABSTRACT FROM AUTHOR]

Electroencephalography in the setting of hypothermia and anoxia has been studied in humans since the 1950s. Specific patterns after cardiac arrest have been associated with prognosis since the 1960s, with several prognostic rating scales developed in the second half of the twentieth century. In 2002, two pivotal clinical trials were published, demonstrating improved neurologic outcomes in patients treated with therapeutic hypothermia (TH) after cardiac arrest of shockable rhythms. In the following years, TH became the standard of care in these patients. During the same time period, the use of continuous EEG monitoring in critically ill patients increased, which led to the recognition of subclinical seizures occurring in patients after cardiac arrest. As a result of these changes, greater amounts of EEG data are being collected, and the significance of specific patterns is being re-explored. We review the current role of EEG for the identification of seizures and the estimation of prognosis after cardiac resuscitation. [ABSTRACT FROM AUTHOR]

Background: Sedation and analgesia regimens during targeted temperature management (TTM), after cardiac arrest varies widely, are poorly described in the literature and may have a negative impact on outcome. Since implementing TTM in 2005, we have used moderate-dose sedation and describe our experience with this approach. Methods: In this retrospective review, we included patients treated with TTM for cardiac arrest at our institution for 2008-2012. Patients received TTM if they did not follow verbal commands following cardiac arrest, regardless of place of arrest or rhythm. Utstein-compatible data were prospectively entered into the International Cardiac Arrest Registry, supplemented by review of nursing, pharmacy, and physical therapy records. We report analgesic and sedative medications and doses during the 24 h of active TTM at 33 °C, resource utilization, and important clinical events. Results: 166 patients treated with TTM after in- and out-of-hospital cardiac arrest with complete data were included. Overall survival was 42 %, median time to following commands was 3 h after rewarming (-6, 14), time to spontaneous breathing trial was 19 h (5-35), time to extubation was 28 h (9-60), and 59 % of survivors were discharged directly home at 13 (10-20) days. The incidence of seizure was 6 %, septic shock 4 %, and pneumonia 32 %. Four survivors required tracheostomy at 8, 8, 12, and 16 days. Conclusions: A moderate-dose sedation and analgesia regimen was well tolerated and effective during therapeutic hypothermia after cardiac arrest and is an effective alternative to very deep sedation. We recommend more complete description of sedation and analgesia protocols in future studies, including expanded outcome reporting to include variables affected by sedation therapy. Further study is required to define which sedation approach for TTM may be best. [ABSTRACT FROM AUTHOR]

Background: Global cerebral edema (GCE) with subsequent refractory intracranial hypertension complicates some cases of aneurysmal subarachnoid hemorrhage (aSAH), and typically is associated with poorer outcome. Treatment options for refractory intracranial pressure (ICP) cases are limited to decompressive hemicraniectomy (DHC) and targeted temperature management (TTM) with induced hypothermia (32-34 °C). No outcomes comparison between patients treated with either or both forms of refractory ICP therapy exists, and data on the effect of prolonged hypothermia on ICP and organ function among patients with aSAH are limited. Methods: This is a retrospective study of aSAH patients who underwent DHC and/or prolonged hypothermia (greater than 48 h) for refractory ICP (i.e., ICP >20 mmHg after osmotherapy) in the intensive care unit of a single, tertiary-care academic center. Results: Nineteen individuals with aSAH underwent TTM with or without DHC; sixteen patients underwent DHC alone. The patients in TTM group were younger (median age 44 years) than the DHC without TTM population (median age 60 years). TTM was started on median day 2 with a median duration of 7 days. There were no significant group differences in survival to discharge (59 % vs. 69 %) or in the mean modified Rankin score on follow-up (3.6 vs. 3.7), despite the TTM group having longer hospital length of stay (24 vs. 19 days, p = 0.03), longer duration of mechanical ventilation (20 vs. 9 days, p = 0.04), a higher cumulative fluid balance (12.8 vs. 5.1 L, p = 0.01), and higher APACHEII scores. The median maximal ICP decreased from 23.5 to 21 mmHg within 24 h of hypothermia initiation. There were no significant differences in other markers of end-organ function (respiratory, hematologic, renal, liver, and cardiac), infection rate, or adverse events between groups. Conclusions: Use of prolonged TTM among aSAH patients with GCE and refractory ICP elevations is associated with a longer duration of mechanical ventilation but is not different in terms of neurological outcomes measured by modified Rankin score or organ function outcomes compared to patients who received DHC alone. [ABSTRACT FROM AUTHOR]

Introduction: Endovascular cooling is currently used for hypothermia treatment and fever reduction therapy. At the same time, little is known about the risks associated to endovascular cooling in patients treated with an endovascular cooling catheter (ECC). Methods: A retrospective chart review of 122 patients with subarachnoid hemorrhage (SAH) treated with an ECC either for therapeutic hypothermia or for fever reduction was performed. ECC-associated thromboembolic events (TEE) such as pulmonary embolism and thrombosis were recorded and compared between patients treated with an ECC and patients treated only with a central venous line (CVL). Additionally, various laboratory parameters were recorded to determine if they might be related to the frequency of TEE's. Results: 43 Patients were treated with an ECC and 79 with a CVL. Patients in the ECC group suffered more frequently from TEE (37 %) than those with a CVL (5 %). None of the laboratory parameters was associated with an increased TEE risk. The treatment with an ECC alone was a risk factor for a TEE, independent from age as well as from Hunt and Hess grade. Conclusion: Our data show that the treatment with ECC increases the risk of TEE in SAH patients. Therefore, especially when considered for fever reduction, non-invasive devices for surface cooling should be the first choice. [ABSTRACT FROM AUTHOR]

Background: Sedation and therapeutic hypothermia (TH) delay neurological responses and might reduce the accuracy of clinical examination to predict outcome after cardiac arrest (CA). We examined the accuracy of quantitative pupillary light reactivity (PLR), using an automated infrared pupillometry, to predict outcome of post-CA coma in comparison to standard PLR, EEG, and somato-sensory evoked potentials (SSEP). Methods: We prospectively studied over a 1-year period (June 2012-June 2013) 50 consecutive comatose CA patients treated with TH (33 °C, 24 h). Quantitative PLR (expressed as the % of pupillary response to a calibrated light stimulus) and standard PLR were measured at day 1 (TH and sedation; on average 16 h after CA) and day 2 (normothermia, off sedation: on average 46 h after CA). Neurological outcome was assessed at 90 days with Cerebral Performance Categories (CPC), dichotomized as good (CPC 1-2) versus poor (CPC 3-5). Predictive performance was analyzed using area under the ROC curves (AUC). Results: Patients with good outcome [ n = 23 (46 %)] had higher quantitative PLR than those with poor outcome [ n = 27; 16 (range 9-23) vs. 10 (1-30) % at day 1, and 20 (13-39) vs. 11 (1-55) % at day 2, both p < 0.001]. Best cut-off for outcome prediction of quantitative PLR was <13 %. The AUC to predict poor outcome was higher for quantitative than for standard PLR at both time points (day 1, 0.79 vs. 0.56, p = 0.005; day 2, 0.81 vs. 0.64, p = 0.006). Prognostic accuracy of quantitative PLR was comparable to that of EEG and SSEP (0.81 vs. 0.80 and 0.73, respectively, both p > 0.20). Conclusions: Quantitative PLR is more accurate than standard PLR in predicting outcome of post-anoxic coma, irrespective of temperature and sedation, and has comparable prognostic accuracy than EEG and SSEP. [ABSTRACT FROM AUTHOR]

Background: Reactive electroencephalography (EEG) background during therapeutic hypothermia (TH) is related to favorable prognosis after cardiac arrest (CA), but its predictive value is not 100 %. The aim of this study was to investigate outcome predictors after a first reactive EEG recorded during TH after CA. Methods: We studied a cohort of consecutive comatose adults admitted between February 2008 and November 2012, after successful resuscitation from CA, selecting patients with reactive EEG during TH. Outcome was assessed at three months, and categorized as survivors and non-survivors (no patient was in vegetative state). Demographics, clinical variables, EEG features, serum neuron-specific enolase (NSE) and procalcitonin, were compared using uni- and multivariable analyses. Results: A total of 290 patients were treated with TH after cardiac arrest; 146 had an EEG during TH, which proved reactive in 90 of them; 77 (86 %) survived and 13 (14 %) died (without recovery from coma). The group of non-survivors had a higher occurrence of discontinuous EEG ( p = 0.006; multivariate analysis p = 0.026), and a higher serum NSE peak ( p = 0.021; multivariate analysis p = 0.014); conversely, demographics, and other clinical variables including serum procalcitonin did not differ. Conclusions: A discontinuous EEG and high serum NSE are associated with mortality after CA in patients with poor outcome despite a reactive hypothermic EEG. This suggests more severe cerebral damage, but not to higher extent of systemic disease. [ABSTRACT FROM AUTHOR]

Background: Perihemorrhagic edema (PHE) develops after intracerebral hemorrhage (ICH). It can worsen the clinical situation by its additional mass effect. Therapeutic hypothermia (TH) might be an effective method to control PHE, but has not been sufficiently studied in ICH patients. Methods: We report data on n = 25 consecutive patients with large supratentorial ICH (volume > 25 ml) who were treated by mild TH of 35 °C for 8-10 days. Body temperature was controlled by endovascular cooling catheters. We followed the clinical course during hospital stay and measured volumes of ICH and PHE in regularly performed serial cranial computed tomography. Outcome was assessed after 3 and 12 months. These data were compared to a historical group of n = 25 patients with large ICH. Results: While PHE continuously increased in the historical control group up to day 10, PHE volumes in the hypothermia group remained stable. There was a significant difference from day 3 after symptom onset. Shivering (36 %) and pneumonia (96 %) were the most frequent complications during TH. Mortality rate was 8.3 % in TH versus 16.7 % in the control group after 3 months and 28 versus 44 % after 1 year. Conclusions: These data support the promising results of our first case series on TH in large ICH. TH prevents the development of PHE and its complications. Side effects of TH appeared often, but could be treated sufficiently. Therefore, TH might represent a new therapy for PHE after large ICH, but has to be further tested in randomized trials. [ABSTRACT FROM AUTHOR]

Background: The objectives of this study were to determine effects of severe traumatic brain injury (TBI) on cerebrospinal fluid (CSF) concentrations of myelin basic protein (MBP) and to assess relationships between clinical variables and CSF MBP concentrations. Methods: We measured serial CSF MBP concentrations in children enrolled in a randomized controlled trial evaluating therapeutic hypothermia (TH) after severe pediatric TBI. Control CSF was obtained from children evaluated, but found not to be having CNS infection. Generalized estimating equation models and Wilcoxon Rank-Sum test were used for comparisons of MBP concentrations. Results: There were 27 TBI cases and 57 controls. Overall mean (±SEM) TBI case MBP concentrations for 5 days after injury were markedly greater than controls (50.49 ± 6.97 vs. 0.11 ± 0.01 ng/ml, p < 0.01). Mean MBP concentrations were lower in TBI patients <1 year versus >1 year (9.18 ± 1.67 vs. 60.22 ± 8.26 ng/ml, p = 0.03), as well as in cases with abusive head trauma (AHT) versus non-abusive TBI (14.46 ± 3.15 vs. 61.17 ± 8.65 ng/ml, p = 0.03). TH did not affect MBP concentrations. Conclusions: Mean CSF MBP increases markedly after severe pediatric TBI, but is not affected by TH. Infancy and AHT are associated with low MBP concentrations, suggesting that age-dependent myelination influences MBP concentrations after injury. Given the magnitude of MBP increases, axonal injury likely represents an important therapeutic target in pediatric TBI. [ABSTRACT FROM AUTHOR]

Background: MRI-based prognostication of comatose cardiac arrest survivors has shown promising results. However, the technique has not been validated in patients treated with therapeutic hypothermia and it is unknown how it might add to NSE-based prognostication. We sought to evaluate the prognostic performance of regional apparent diffusion coefficient (ADC) in comatose out-of-hospital cardiac arrest (OHCA) patients treated with mild hypothermia and its added value to NSE-based prognostication. Methods: An OHCA registry was analyzed to identify OHCA patients older than 15 who were treated with therapeutic hypothermia and underwent brain MRI between 2008 and 2011. Quantitative measurement of regional ADCs was performed by a radiologist blinded to the clinical outcome. Results: Of the 43 eligible patients, 11 (18.6 %) achieved a good outcome (6-month CPC of 1 or 2). The regional ADC of the occipital cortex showed the highest discriminatory power with an area under the curve of receiver operating characteristic (AUROC) of 0.943 (95 % CI, 0.872-1.000) and predicted poor outcomes with a sensitivity of 90.6 % and a specificity of 100 %. The AUROC for NSE levels (48-h) was 0.911 (95 % CI, 0.801-1.000) which was significantly correlated with the regional ADC (Pearson's r = −0.674, p < .001). The ADC-based predictions identified an additional 5 (35.7 %) poor outcome patients out of 14 with 48-h NSE levels less than 78.9 ng/mL, which is the cutoff point suggested in a previous study. However, additional prognostic information was not provided when the 48-h NSE levels were >78.9 ng/mL. Conclusions: Regional ADC-based prognostication was accurate in OHCA patients who were treated with mild hypothermia. However, it only provided additional prognostic information when the 48-h NSE levels indicated a good prognosis (48-h NSE <78.9 ng/mL). [ABSTRACT FROM AUTHOR]

Cardiac arrest is the most common cause of death in North America. Neurocritical care interventions, including therapeutic hypothermia (TH), have significantly improved neurological outcomes in patients successfully resuscitated from cardiac arrest. Therefore, resuscitation following cardiac arrest was chosen as an Emergency Neurological Life Support protocol. Patients remaining comatose following resuscitation from cardiac arrest and who are not bleeding are potential candidates for TH. This protocol will review induction, maintenance, and re-warming phases of TH, along with management of TH side effects. Aggressive shivering suppression is necessary with this treatment to ensure the maintenance of a target temperature. Ancillary testing, including electrocardiography, computed tomography imaging of the brain, continuous electroencephalography, monitoring, and correction of electrolyte, blood gas, and hematocrit changes are also necessary to optimize outcomes. [ABSTRACT FROM AUTHOR]

The loss of the N20 component on testing median somatosensory evoked potentials (SSEP) has been established as the most reliable indicator of unfavorable prognosis in post-cardiopulmonary arrest patients. With the intervention of therapeutic hypothermia in the management of patients who remain comatose following cardiopulmonary arrest that association is now in dispute. Abandoning SSEP as a key prognostic indicator of neurologic outcome would be a serious loss and cannot be justified. [ABSTRACT FROM AUTHOR]

Background: Although the benefits of mild therapeutic hypothermia (MTH) in selected patients after out-of-hospital cardiac arrest have been consistently demonstrated, no controlled trial of MTH in selected patients after in-hospital cardiac arrest (IHCA) has been published. We sought to assess the benefit of MTH after IHCA in patients meeting our institutions IHCA MTH inclusion criteria. Methods: A retrospective, historical control study was performed. During the 3-year period before and after the 2006 MTH protocol implementation at our institution, we identified a total of 118 patients admitted to our Medical Intensive Care Unit after resuscitation from an IHCA. Two blinded investigators identified all patients meeting our institutions MTH protocol inclusion criteria and the patients in each time period were compared. The primary outcome was discharge with good neurological function. Results: 33 IHCA patients met MTH protocol inclusion criteria; 16 patients were admitted prior to MTH protocol implementation and thus were not treated with MTH post arrest while 17 patients were admitted after implementation and were all treated with MTH post arrest. 91% of patients had an arrest rhythm of asystole or pulseless electrical activity. Good neurological function at discharge was found in 24% of MTH patients and 31% of controls ( P = .62). Conclusions: No difference in neurological outcome at discharge was detected in predominantly non-shockable IHCA patients treated with MTH. This finding, if confirmed with further study, may define a population of patients for whom this costly and resource intensive therapy should be withheld. [ABSTRACT FROM AUTHOR]

Background: Therapeutic hypothermia is a promising neuroprotective therapy with multiple mechanisms of action. We demonstrated the feasibility of thrombolysis combined with endovascular hypothermia, but not all patients achieved effective cooling. We sought to identify the factors that determined effective cooling. Methods: In 26 patients who underwent endovascular hypothermia, we computed four measures of effective cooling: time to reach target; Area-Under-the-Curve (AUC) 34 ratio; AUC-34; and AUC-35. By multivariate regression, we examined the effects of age, weight, starting temperature, body mass index, body surface area (BSA), gender, shivering, and total meperidine dose on the four outcome measures. Results: In univariate analyses, all four outcome measures were significantly influenced by BSA ( p < 0.01 in all univariate analyses). Time to reach target temperature was quicker in older patients ( p < 0.01). Shivering and meperidine dose were highly intercorrelated ( r = 0.6, p < 0.01) and both marginally influenced all four outcome measures. In multivariate analysis, AUC ratio and time to reach target temperature were significantly influenced by BSA ( p < 0.01) and meperidine ( p < 0.05); AUC-34 was influenced only by BSA ( p < 0.01). The AUC-35 was influenced by BSA ( p < 0.01), shivering, and total meperidine dose ( p < 0.05). Conclusions: The most important determinant of effective cooling during endovascular hypothermia is BSA; larger patients are more difficult to cool and maintain in therapeutic range. Older patients cool more quickly. Shivering was well controlled by the combination of meperidine, buspirone, and surface counter-warming and only minimally influenced cooling effectiveness. Future trials of therapeutic hypothermia may include added measures to cool larger patients more effectively. [ABSTRACT FROM AUTHOR]

Background: Despite the advances in critical care, severe viral meningoencephalitis continues to impose high rates of morbidity and mortality. Consequently, new treatment strategies are needed and we present therapeutic hypothermia (TH) as one of the possible efficacious treatment tools. Methods: We present the case series in an adult intensive care unit of a tertiary care hospital. Eleven patients suffering from severe viral meningoencephalitis were treated with hypothermia. The major indication for TH was severely impaired consciousness associated with carbon dioxide reactivity loss assessed by Transcranial Doppler. Besides from the established treatment, all the patients underwent TH. Mild hypothermia (rectal temperature of 32-34°C) was maintained with continuous veno-venous hemofiltration. Results: Median Glasgow coma scale score in our patients at admission was 8 (3-10) and median Acute Physiology and Chronic Health Evaluation score was 24 (12-32). The overall mortality rate was 9% (1/11). Among survivors, the outcome was favorable in five patients [Glasgow Outcome Scale score (GOS) 4-5]. Remaining five patients had severe residual neurological deficit (GOS 3). Median GCS at discharge was 15 (8-15). With respect to disease severity, the outcome in presented patients was generally satisfactory. Conclusions: Our results suggest that use of mild hypothermia in selected adult patients with viral meningoencephalitis could be a promising treatment tool. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Effectiveness of cooling and adverse events (AEs) involving skin have not been intensively evaluated in cardiac arrest survivors treated with therapeutic hypothermia (TH) when induced and maintained with a servomechanism-regulated surface cooling system. Methods: Retrospective review of sixty-nine cardiac arrest survivor-events admitted from April 2006-September 2008 who underwent TH using the Medivance Arctic Sun Temperature Management System. A TH database and medical records were reviewed, and nursing interviews conducted. Primary endpoint was time from initiation to target temperature (TT; 32-34°C). Secondary endpoints were cooling rate, percentage of hypothermia maintenance phase at TT, effect of body-mass index (BMI) on rate of cooling, and AEs. Results: Mean time to the target temperature (TT) was 2.78 h; 80% of patients achieved TT within 4 h; all did within 8 h. Patients were at TT for 96.7% of hypothermia maintenance; 17% of patients had >1 hourly temperature measurement outside TT range. Mean cooling rate during induction phase was 1.1°C/h, and was not associated with BMI. Minor skin injury occurred in 14 (20%) patients; 4 (6%) were device-related. Skin injuries were associated with shock ( P = 0.04), and decubitus ulcers were associated with left ventricular ejection fraction <45% ( P = 0.004). AEs included shivering (94%), hypokalemia (81%), hyperglycemia (57%), pneumonia (23%), bleeding (22%), post-cooling fever (17%), and bacteremia (9%). Conclusions: The Arctic Sun Temperature Management System was an effective means of performing therapeutic hypothermia after cardiac arrest. Infrequent skin injuries were associated with vasopressor use and low ejection fraction. [ABSTRACT FROM AUTHOR]

Background: Electroencephalographic (EEG) features may provide objective data regarding prognosis in children resuscitated from cardiac arrest (CA), but therapeutic hypothermia (TH) may impact its predictive value. We aimed to determine whether specific EEG features were predictive of short-term outcome in children treated with TH after CA, both during hypothermia and after return to normothermia. Methods: Thirty-five children managed with a standard clinical TH algorithm after CA were prospectively enrolled. EEG recordings were scored in a standardized manner and categorized. EEG category 1 consisted of continuous and reactive tracings. EEG category 2 consisted of continuous but unreactive tracings. EEG category 3 included those with any degree of discontinuity, burst suppression, or lack of cerebral activity. The primary outcome was unfavorable short-term outcome defined as Pediatric Cerebral Performance Category score of 4-6 (severe disability, vegetative, death) at hospital discharge. Univariate analyses of the association between EEG category and outcome was performed using logistic regression. Results: For tracings obtained during hypothermia, patients with EEGs in categories 2 or 3 were far more likely to have poor outcome than those in category 1 (OR 10.7, P = 0.023 and OR 35, P = 0.004, respectively). Similarly, for tracings obtained during normothermia, patients with EEGs in categories 2 or 3 were far more likely to have poor outcomes than those in category 1 (OR 27, P = 0.006 and OR 18, P = 0.02, respectively). Conclusions: A simple EEG classification scheme has predictive value for short-term outcome in children undergoing TH after CA. [ABSTRACT FROM AUTHOR]

Experimental evidence and clinical experience suggest that mild hypothermia protects numerous tissues from damage during ischemic insult. However, the extent to which hypothermia becomes a valued therapeutic option will depend on the clinician's ability to rapidly reduce core body temperature and safely maintain hypothermia. To date, general anesthesia is the best way to block autonomic defenses during induction of mild-to-moderate hypothermia; unfortunately, general anesthesia is not an option in most patients likely to benefit from therapeutic hypothermia. Induction of hypothermia in awake humans is complicated by both the technical difficulties related to thermal manipulation and the remarkable efficacy of thermoregulatory defenses, especially vasoconstriction and shivering. The most effective thermal manipulation devices are generally invasive and, therefore, more prone to complications than surface methods. In an effort to inhibit thermoregulation in awake humans, several agents have been tested either alone or in combination with each other. For example, the combination of meperidine and buspirone has already been applied to facilitate induction of hypothermia in human trials. However, pharmacological induction of thermoregulatory tolerance to cold without excessive sedation, respiratory depression, or other serious toxicity remains a major focus of current therapeutic hypothermia research. [ABSTRACT FROM AUTHOR]