David B. Seder

Transcranial Doppler for predicting delayed cerebral ischemia after subarachnoid hemorrhage.

OBJECTIVETranscranial Doppler (TCD) is widely used to monitor the temporal course of vasospasm after subarachnoid hemorrhage (SAH), but its ability to predict clinical deterioration or infarction from delayed cerebral ischemia (DCI) remains controversial. We sought to determine the prognostic utility of serial TCD examination after SAH. METHODSWe analyzed 1877 TCD examinations in 441 aneurysmal SAH patients within 14 days of onset. The highest mean blood flow velocity (mBFV) value in any vessel before DCI onset was recorded. DCI was defined as clinical deterioration or computed tomographic evidence of infarction caused by vasospasm, with adjudication by consensus of the study team. Logistic regression was used to calculate adjusted odds ratios for DCI risk after controlling for other risk factors. RESULTSDCI occurred in 21% of patients (n = 92). Multivariate predictors of DCI included modified Fisher computed tomographic score (P = 0.001), poor clinical grade (P = 0.04), and female sex (P = 0.008). After controlling for these variables, all TCD mBFV thresholds between 120 and 180 cm/s added a modest degree of incremental predictive value for DCI at nearly all time points, with maximal sensitivity by SAH day 8. However, the sensitivity of any mBFV more than 120 cm/s for subsequent DCI was only 63%, with a positive predictive value of 22% among patients with Hunt and Hess grades I to III and 36% in patients with Hunt and Hess grades IV and V. Positive predictive value was only slightly higher if mBFV exceeded 180 cm/s. CONCLUSIONIncreased TCD flow velocities imply only a mild incremental risk of DCI after SAH, with maximal sensitivity by day 8. Nearly 40% of patients with DCI never attained an mBFV more than 120 cm/s during the course of monitoring. Given the poor overall sensitivity of TCD, improved methods for identifying patients at high risk for DCI after SAH are needed.

Early cardiac catheterization is associated with improved survival in comatose survivors of cardiac arrest without STEMI

AIM To determine if early cardiac catheterization (CC) is associated with improved survival in comatose patients who are resuscitated after cardiac arrest when electrocardiographic evidence of ST-elevation myocardial infarction (STEMI) is absent. METHODS We conducted a retrospective observational study of a prospective cohort of 754 consecutive comatose patients treated with therapeutic hypothermia (TH) following cardiac arrest. RESULTS A total of 269 (35.7%) patients had cardiac arrest due to a ventricular arrhythmia without STEMI and were treated with TH. Of these, 122 (45.4%) received CC while comatose (early CC). Acute coronary occlusion was discovered in 26.6% of patients treated with early CC compared to 29.3% of patients treated with late CC (p=0.381). Patients treated with early CC were more likely to survive to hospital discharge compared to those not treated with CC (65.6% vs. 48.6%; p=0.017). In a multivariate regression model that included study site, age, bystander CPR, shock on admission, comorbid medical conditions, witnessed arrest, and time to return of spontaneous circulation, early CC was independently associated with a significant reduction in the risk of death (OR 0.35, 95% CI 0.18-0.70, p=0.003). CONCLUSIONS In comatose survivors of cardiac arrest without STEMI who are treated with TH, early CC is associated with significantly decreased mortality. The incidence of acute coronary occlusion is high, even when STEMI is not present on the postresuscitation electrocardiogram.

Predictors of long-term shunt-dependent hydrocephalus after aneurysmal subarachnoid hemorrhage. Clinical article.

OBJECT The purpose of this study was to identify predictors of shunt-dependent hydrocephalus after aneurysmal subarachnoid hemorrhage (SAH). METHODS The authors evaluated the incidence of shunt-dependent hydrocephalus in a consecutive cohort of 580 patients with SAH who were admitted to the Neurological Intensive Care Unit of Columbia University Medical Center between July 1996 and September 2002. Patient demographics, 24-hour admission variables, initial CT scan characteristics, daily transcranial Doppler variables, and development of in-hospital complications were analyzed. Odds ratios and 95% CIs for candidate predictors were calculated using multivariate nominal logistic regression. RESULTS Admission glucose of at least 126 mg/dl (adjusted OR 1.6; 95% CI 1.0-2.6), admission brain CT scan with a bicaudate index of at least 0.20 (adjusted OR 1.43; 95% CI 1.0-2.0), Fisher Grade 4 (adjusted OR 2.71; 95% CI 1.2-5.7), fourth ventricle hemorrhage (adjusted OR 1.78; 95% CI 1.1-2.7), and development of nosocomial meningitis (adjusted OR 2.2; 95% CI 1.4-3.7) were independently associated with shunt dependency. CONCLUSIONS These data suggest that permanent CSF diversion after aneurysmal SAH may be independently predicted by hyperglycemia at admission, findings on the admission CT scan (Fisher Grade 4, fourth ventricle intraventricular hemorrhage, and bicaudate index ≥ 0.20), and development of nosocomial meningitis. Future research is needed to assess if tight glycemic control, reduction of fourth ventricle clot burden, and prevention of nosocomial meningitis may reduce the need for permanent CSF diversion after aneurysmal SAH.

Methods of cooling: practical aspects of therapeutic temperature management.

Objectives:To review traditional and newer means of inducing, maintaining, and withdrawing therapeutic hypothermia and normothermia. To suggest treatment algorithms for temperature modulation and review neuromonitoring options. Design:A review of current literature describing methods of performing therapeutic temperature management and neuromonitoring during the cooling, maintenance, and decooling periods. Algorithms for performing therapeutic temperature management are suggested. Results:Temperature management can be safely and effectively performed using traditional or newer modalities. Although traditional means of cooling are feasible and efficacious, modern devices utilizing feedback loops to maintain steady body temperature and prevent overcooling have advantages in ease of application, patient safety, maintenance of target temperature, and control of decooling. Neuromonitoring options should be adapted to an individual patient and situation. Conclusions:Intensivists should be familiar with techniques to induce, maintain, and withdraw therapeutic temperature management, and select the most appropriate method for a given patient and situation.

Single-dose etomidate is not associated with increased mortality in ICU patients with sepsis: analysis of a large electronic ICU database.

Objective:Retrospective analyses of several trials suggest etomidate may be unsafe for intubation in patients with sepsis. We evaluated the association of etomidate and mortality in a large cohort of septic patients to determine if single-dose etomidate was associated with increased in-hospital mortality. Design and Setting:Retrospective cohort study at the Philips eICU Research Institute ICU clinical database. Interventions:None. Patients:Among 741,036 patients monitored from 2008 through 2010, we identified 2,014 adults intubated in the ICU 4–96 hrs after admission, having clinical criteria consistent with sepsis, severe sepsis, or septic shock. In all, 1,102 patients received etomidate and 912 received other induction agents for intubation. Measurements and Main Results:The primary endpoint was in-hospital mortality, but we also evaluated demographic and clinical factors, severity of illness, ICU mortality, ICU length of stay, hospital length of stay, ventilator days, and vasopressor days. Competing risk Cox proportional hazard regression models were used for primary outcomes. Demographics and illness severity were similar between the groups. Hospital mortality was similar between the groups (37.2% vs. 37.8%, p = 0.77), as were ICU mortality (30.1% vs. 30.2%, p = 0.99), ICU length of stay (8.7 days vs. 8.9 days, p = 0.66), and hospital length of stay (15.2 vs. 14.6 days, p = 0.31). More patients in the etomidate group received steroids before and after intubation (52.9% vs. 44.5%, p < 0.001), but vasopressor use and duration of mechanical ventilation were similar. No regression model showed an independent association of etomidate with mortality, shock, duration of mechanical ventilation, ICU or hospital length of stay, or vasopressor use. A hospital mortality model limited to only patients with septic shock (n = 650) also showed no association of etomidate and hospital mortality. Conclusion:In a mixed-diagnosis group of critically ill patients with sepsis, severe sepsis, and septic shock, single-dose etomidate administration for intubation in the ICU was not associated with higher mortality or other adverse clinical outcomes.

The Insertion and Management of External Ventricular Drains: An Evidence-Based Consensus Statement : A Statement for Healthcare Professionals from the Neurocritical Care Society.

Abstract External ventricular drains (EVDs) are commonly placed to monitor intracranial pressure and manage acute hydrocephalus in patients with a variety of intracranial pathologies. The indications for EVD insertion and their efficacy in the management of these various conditions have been previously addressed in guidelines published by the Brain Trauma Foundation, American Heart Association and combined committees of the American Association of Neurological Surgeons and the Congress of Neurological Surgeons. While it is well recognized that placement of an EVD may be a lifesaving intervention, the benefits can be offset by procedural and catheter-related complications, such as hemorrhage along the catheter tract, catheter malposition, and CSF infection. Despite their widespread use, there are a lack of high-quality data regarding the best methods for placement and management of EVDs to minimize these risks. Existing recommendations are frequently based on observational data from a single center and may be biased to the authors’ view. To address the need for a comprehensive set of evidence-based guidelines for EVD management, the Neurocritical Care Society organized a committee of experts in the fields of neurosurgery, neurology, neuroinfectious disease, critical care, pharmacotherapy, and nursing. The Committee generated clinical questions relevant to EVD placement and management. They developed recommendations based on a thorough literature review using the Grading of Recommendations Assessment, Development, and Evaluation system, with emphasis placed not only on the quality of the evidence, but also on the balance of benefits versus risks, patient values and preferences, and resource considerations.

Outcomes of Comatose Cardiac Arrest Survivors With and Without ST-Segment Elevation Myocardial Infarction: Importance of Coronary Angiography

OBJECTIVES The aim of this study was to compare outcomes and coronary angiographic findings in post-cardiac arrest patients with and without ST-segment elevation myocardial infarction (STEMI). BACKGROUND The 2013 STEMI guidelines recommend performing immediate angiography in resuscitated patients whose initial electrocardiogram shows STEMI. The optimal approach for those without STEMI post-cardiac arrest is less clear. METHODS A retrospective evaluation of a post-cardiac arrest registry was performed. RESULTS The database consisted of 746 comatose post-cardiac arrest patients including 198 with STEMI (26.5%) and 548 without STEMI (73.5%). Overall survival was greater in those with STEMI compared with those without (55.1% vs. 41.3%; p = 0.001), whereas in all patients who underwent immediate coronary angiography, survival was similar between those with and without STEMI (54.7% vs. 57.9%; p = 0.60). A culprit vessel was more frequently identified in those with STEMI, but also in one-third of patients without STEMI (80.2% vs. 33.2%; p = 0.001). The majority of culprit vessels were occluded (STEMI, 92.7%; no STEMI, 69.2%; p < 0.0001). An occluded culprit vessel was found in 74.3% of STEMI patients and in 22.9% of no STEMI patients. Among cardiac arrest survivors discharged from the hospital who had presented without STEMI, coronary angiography was associated with better functional outcome (93.3% vs. 78.7%; p < 0.003). CONCLUSIONS Early coronary angiography is associated with improved functional outcome among resuscitated patients with and without STEMI. Resuscitated patients with a presumed cardiac etiology appear to benefit from immediate coronary angiography.

Neurologic Outcomes and Postresuscitation Care of Patients With Myoclonus Following Cardiac Arrest.

Objectives: To evaluate the outcomes of cardiac arrest survivors with myoclonus receiving modern postresuscitation care. Design: Retrospective review of registry data. Setting: Cardiac arrest receiving centers in Europe and the United States from 2002 to 2012. Patients: Two thousand five hundred thirty-two cardiac arrest survivors 18 years or older enrolled in the International Cardiac Arrest Registry. Interventions: None. Measurements and Main Results: Eighty-eight percent of patients underwent therapeutic hypothermia and 471 (18%) exhibited myoclonus. Patients with myoclonus had longer time to professional cardiopulmonary resuscitation (8.6 vs 7.0 min; p < 0.001) and total ischemic time (25.6 vs 22.3 min; p < 0.001) and less often presented with ventricular tachycardia/ventricular fibrillation, a witnessed arrest, or had bystander cardiopulmonary resuscitation. Electroencephalography demonstrated myoclonus with epileptiform activity in 209 of 374 (55%), including status epilepticus in 102 of 374 (27%). Good outcome (Cerebral Performance Category 1–2) at hospital discharge was noted in 9% of patients with myoclonus, less frequently in myoclonus with epileptiform activity (2% vs 15%; p < 0.001). Patients with myoclonus with good outcome were younger (53.7 vs 62.7 yr; p < 0.001), had more ventricular tachycardia/ventricular fibrillation (81% vs 46%; p < 0.001), shorter ischemic time (18.9 vs 26.4 min; p = 0.003), more witnessed arrests (91% vs 77%; p = 0.02), and fewer “do-not-resuscitate” orders (7% vs 78%; p < 0.001). Life support was withdrawn in 330 of 427 patients (78%) with myoclonus and poor outcome, due to neurological futility in 293 of 330 (89%), at 5 days (3–8 d) after resuscitation. With myoclonus and good outcome, median ICU length of stay was 8 days (5–11 d) and hospital length of stay was 14.5 days (9–22 d). Conclusions: Nine percent of cardiac arrest survivors with myoclonus after cardiac arrest had good functional outcomes, usually in patients without associated epileptiform activity and after prolonged hospitalization. Deaths occurred early and primarily after withdrawal of life support. It is uncertain whether prolonged care would yield a higher percentage of good outcomes, but myoclonus of itself should not be considered a sign of futility.

Geriatric experience following cardiac arrest at six interventional cardiology centers in the United States 2006-2011: interplay of age, do-not-resuscitate order, and outcomes.

Objectives:It is not known if aggressive postresuscitation care, including therapeutic hypothermia and percutaneous coronary intervention, benefits cardiac arrest survivors more than 75 years old. We compared treatments and outcomes of patients at six regional percutaneous coronary intervention centers in the United States to determine if aggressive care of elderly patients was warranted. Design:Retrospective evaluation of registry data. Setting:Six interventional cardiology centers in the United States. Patients:Six hundred and twenty-five unresponsive cardiac arrest survivors aged 18–75 were compared with 129 similar patients aged more than 75. Interventions:None. Measurements and Main Results:Cardiac arrest survivors aged more than 75 had more comorbidities (3.0 ± 1.6 vs 2.0 ± 1.6, p < 0.001), but were matched to younger patients in initial heart rhythm, witnessed arrests, bystander cardiopulmonary resuscitation, and total ischemic time. Patients aged more than 75 frequently underwent therapeutic hypothermia (97.7%), urgent coronary angiography (44.2%), and urgent percutaneous coronary intervention (24%). They had more sustained hyperglycemia (70.5% vs 59%, p = 0.015), less postcooling fever (25.2% vs 35.2%, p = 0.03), were more likely to have do-not-resuscitate orders (65.9% vs 48.2%, p < 0.001), and undergo withdrawal of life support (61.2% vs 47.5%, p = 0.005). Good functional outcome at 6 months (Cerebral Performance Category 1–2) was seen in 27.9% elderly versus 40.4% younger patients overall (p = 0.01) and in 44% versus 55% (p = 0.13) of patients with an initial shockable rhythm. Of 35 survivors more than 75 years old, 33 (94.8%) were classified as Cerebral Performance Category 1 or 2 at (mean) 6.5-month follow-up. In multivariable logistic regression modeling, age more than 75 was significantly associated with outcome only when the presence of a do-not-resuscitate order was excluded from the model. Conclusions:Elderly patients were more likely to have do-not-resuscitate orders and to undergo withdrawal of life support. Age was independently associated with outcome only when correction for do-not-resuscitate status was excluded, and functional outcomes of elderly survivors were similar to younger patients. Exclusion of patients more than 75 years old from aggressive care is not warranted on the basis of age alone.

Prothrombin complex concentrates to reverse warfarin-induced coagulopathy in patients with intracranial bleeding.

Prothrombin complex concentrates (PCCs) offer a means for the rapid reversal of warfarin, particularly in the setting of life-threatening bleeding. We evaluated the effectiveness and safety of a PCC-based protocol in patients with warfarin-associated intracerebral hemorrhage (ICH), subdural hematoma (SDH), or subarachnoid hemorrhage (SAH). This was a retrospective case-series review of patients treated with an institution-approved warfarin reversal protocol. Patients with intracranial hemorrhage and known warfarin use with an international normalized ratio (INR)>1.4 received fresh frozen plasma (FFP), vitamin K (phytonadione), and weight-based, 3-factor PCC (Profilnine(®) SD) dose based on the initial INR. Demographic and clinical information, the degree of and time to INR normalization, and adverse events were recorded. The thirty study patients included 19 with primary ICH, 7 with SDH, and 4 with SAH. The mean age was 72.8 (±11) years, including 11 (37%) patients ≥80years old. The median presenting INR was 2.3 (IQR 2-3.3) and post-treatment INR was 1.4 (IQR 1.3-1.5, Z score 6.4, p<0.001). Median time from PCC administration to the first follow up INR was 95 (IQR 50-140) min. No patients INR increased by more than 0.3 over 72h. Nine patients (30%) underwent neurosurgical procedures after PCC administration and no procedure-related bleeding complication was noted. Adverse events included 3 instances of early hematoma expansion, one ischemic stroke in a patient with endocarditis on post-PCC day 1, one pulmonary embolism 5weeks after PCC treatment, and one coronary in-stent thrombosis 60days after PCC treatment. 6 patients died prior to hospital discharge of anticipated complications of their initial event, and none from identifiable thrombotic complications of PCC. A 3-factor PCC preparation (Profilnine(®) SD), administered with FFP and vitamin K to patients with acute warfarin-associated intracranial bleeding is a reasonable approach to urgent warfarin reversal. However, randomized, prospective trials are needed to verify the safety and clinical effectiveness of PCC administration in this population.