Safety, tolerability, and pharmacokinetics of weight-based IV loading dose of lacosamide in the ICU.

Among the newer antiseizure medications, lacosamide (LCM) has been increasingly used for acute seizures and status epilepticus in intensive care unit (ICU). We reviewed retrospectively weight-based dosing of IV LCM in patients admitted to ICU with acute seizures and status epilepticus. We have analyzed 354/382 patient treated with IV LCM in ICU during the years 2013-2016. Data collected were age, total body weight, body mass index (BMI), loading dose, post-IV infusion LCM blood level, duration of infusion, blood pressure, heart rate, oxygen saturation, mean arterial pressures, and documented initiation of pressor agents during or within in 30 min of infusion. Larger doses >8 mg/kg of IV LCM that can be safely administered in ICU patients produce effective plasma levels of 15-20 µg/ml with relatively constant volume of distribution.

Secondary hypothermia in patients with super-refractory status epilepticus managed with propofol and ketamine.

BACKGROUND: Therapeutic hypothermia as a potent nonpharmacologic antiseizure therapy has been investigated experimentally in animal models and humans. Although induced hypothermia has been shown to be neuroprotective in acute convulsive status epilepticus, whether its use will translate into improved outcomes for patients with super-refractory nonconvulsive status epilepticus (SRNCSE) has been debated. No clinical data are available on the occurrence and prognostic impact of secondary hypothermia (s-HT) in patients with SRNCSE. With the possibility of core to periphery redistribution of heat with propofol and a centrally mediated dose-dependent fall in body temperature with ketamine, we aimed to investigate the incidence of s-HT events in patients with SRNCSE managed with propofol and ketamine and their impact on clinical outcomes. METHODS: We performed a retrospective observational analysis of consecutive patients with SRNCSE managed with propofol and/or ketamine in a single-center neurological intensive care unit between December 1, 2012 and December 31, 2015. Patients were divided according to the occurrence of hypothermia (temperature < 35.0 °C) into an s-HT group and a nonhypothermia (n-HT) group. Patients who received targeted temperature management therapy were excluded. We compared the demographics, comorbidities, treatment characteristics, and outcomes between groups. RESULTS: Ninety-nine consecutive patients with SRNCSE managed with propofol and/or ketamine were identified during the study period. Twenty patients who received targeted temperature management were excluded, leaving a total of 79 patients for analysis. Hypothermia was observed in 52% (41/79) of the study population. Ketamine was used in 63/79 patients (80%). Ketamine infusion rates were higher and of longer duration among patients who developed s-HT compared with those who did not (mean dosage: 57.35 ±â€¯26.6 mcg/kg/min vs 37.17 ±â€¯15 mcg/kg/min, P = 0.001; duration: 116.36 ±â€¯81.9 h vs 88 ±â€¯89.7 h, P = 0.048). Propofol was used in 78/79 patients (99%), with no significant differences in characteristics between groups (mean dosage: 46.44 ±â€¯20.2 mcg/kg/min vs 36.9 ±â€¯12.9 mcg/kg/min, P = 0.058; duration: 125.43 ±â€¯96.4 h vs 102.3 ±â€¯87.1 h, P = 0.215). No significant differences in demographics, comorbidities, status epilepticus duration and resolution rates, and outcomes were observed between groups. CONCLUSION: In this single-center retrospective analysis of patients whose SRNCSE is being treated, higher doses and longer durations of ketamine were associated with the occurrence of s-HT. Further investigation is warranted to clarify the thermogenic effects of ketamine and its effect on status epilepticus outcomes.

Decompressive hemicraniectomy in the management of subcortical spontaneous intracerebral hemorrhage.

BACKGROUND: The benefit of decompressive hemicraniectomy in patients with malignant acute ischemic stroke is well established, however its role in supratentorial intracerebral hemorrhages is unclear and evolving. Prior studies combined cortical and subcortical hemorrhages in their analysis despite their different natural history. Subcortical hematoma is associated with worse outcomes due to mechanical compression of subcortical structures. We describe outcomes of a matched comparison of patients with spontaneous subcortical hemorrhage managed with hemicraniectomy versus medical management alone. METHODS: Using our "Get-with-the-guideline stroke" database, patients with spontaneous subcortical hematoma managed with hemicraniectomy were identified. Using age, gender, and hematoma volume (categorized as 0-30, 30-60, >60ml), patients managed with hemicraniectomy were matched with medical management alone. Outcomes included hospital length of stay, discharge disposition, and Glasgow outcome score. RESULTS: Eight patients with subcortical hematoma managed with hemicraniectomy were matched with 22 medically managed patients. Other than use of antithrombotics, clinical characteristics did not differ between groups. On comparing outcomes, hospital length of stay in the hemicraniectomy group (26.5 vs 12.5 days p = 0.006) was significantly longer. Discharge disposition did not differ between groups (75% vs 36.4% p = 0.101). Despite a higher frequency of Glasgow outcome score ≥ 3 at 90 days amongst hemicraniectomy cases, there was no significant difference between groups (71.3% vs 54.5% p = 0.535). CONCLUSION: Hemicraniectomy for subcortical hematoma was associated with a prolonged hospital stay. Despite improving survival and favorable discharge disposition, there was no statistically significant difference between groups. Further studies on the benefit of hemicraniectomy in subcortical hematoma are needed.

Massive air embolism resulting in ischemic stroke after left ventricular assist device implantation.

We present the first case of ischemic stroke secondary to massive air embolus during implantation of a left ventricular assist device (LVAD). The patient experienced a suction event at the time of aortic cannula removal. Despite the use of all standard deairing techniques and flooding the operative field with continuous-flow carbon dioxide, a significant amount of air was delivered into the ascending aorta through the LVAD pump.

Ketamine Infusion Used to Successfully Control Refractory Status Epilepticus in a Pregnant Patient.

The management of SE during pregnancy is especially challenging to the treating physician. While antiepileptic medications might cause teratogenicity, SE can have significant morbidity and mortality on both the mother and the developing fetus. This case report demonstrated the successful use of ketamine infusion in the management of RSE in pregnancy without affecting the immediate outcome of pregnancy. The fetus survived this complicated ICU stay and outpatient follow-up was generally uncomplicated. The pregnancy was ended with a delivery of a normal female newborn.

Description of a novel telemedicine-enabled comprehensive system of care: drip and ship plus drip and keep within a system of stroke care delivery.

United States (US) and worldwide telestroke programs frequently focus only on emergency room hyper-acute stroke management. This article describes a comprehensive, telemedicine-enabled, stroke care delivery system that combines "drip and ship" and "drip and keep" models with a comprehensive stroke center primary hub at Ochsner Medical Center in New Orleans, advanced stroke-capable regional hubs, and geographically-aligned, "stroke-ready" spokes. The primary hub provides vascular neurology expertise via telemedicine and monitors care for patients remaining at regional hubs and spokes using a multidisciplinary team approach. By 2014, primary hub telestroke consults grew to ≈1000/year with 16 min average door to consult initiation and 20 min to completion, and 29% of ischemic stroke patients received recombinant tissue-type plasminogen activator (rtPA), increasing 275%. Most patients remained in hospitals close to home, but neurointensive care and interventional procedures were common reasons for primary hub transfer. Given the time sensitivity and expert consultation needed for complex acute stroke care delivery paradigms, telestroke programs are effective for fulfilling unmet care needs. Combining drip and ship and drip and keep management allows more patients to stay "local," limiting primary hub transfer unless more advanced services are required. Post admission telestroke management at spokes increases personnel efficiency and can positively impact stroke outcomes.

Do Not Resuscitate, Anesthesia, and Perioperative Care: A Not So Clear Order.

BACKGROUND: Advance directives guide healthcare providers to listen to and respect patients' wishes regarding their right to die in circumstances when cardiopulmonary resuscitation is required, and hospitals accredited by The Joint Commission are required to have a do-not-resuscitate (DNR) policy in place. However, when surgery and anesthesia are necessary for the care of the patient with a DNR order, this advance directive can create ethical dilemmas specifically involving patient autonomy and the physician's responsibility to do no harm. METHODS: This paper discusses the ethical considerations regarding perioperative DNR orders and provides guidance on how to handle situations that may arise in the conduct of perioperative care. RESULTS: Because of the potential conflicts between ethical care and the restrictions of DNR orders, it is critically important to discuss the medical and ethical issues surrounding this clinical scenario with the patient or surrogate prior to any surgical intervention. However, many anesthesiologists do not adequately address this ethical dilemma prior to the procedure. CONCLUSION: Practitioners are advised to first consider what is best for the patient and, when in doubt, to communicate with patients or surrogates and with colleagues to arrive at the most appropriate care plan. If irreconcilable conflicts arise, consultation with the institution's bioethics committee, if available, is beneficial to help reach a resolution.

Propofol-ketamine combination therapy for effective control of super-refractory status epilepticus.

Retrospective analysis was conducted of patients with SRSE who were treated simultaneously with propofol and ketamine. Sixty-seven patients were identified from 2012 to 2015, and outcomes documented were resolution and mortality. The duration of combined ketamine and propofol use ranged from 1 to 28 days (mean - 3.6 days). Infusion rates ranged up to 145 and 175 mcg/kg/min. Vasopressors were used in 53 patients (79%), and were given within the first 5 days of the ICU admission in 48 (91%) patients. The overall SRSE resolution rate was 91%, and the overall mortality including patients with anoxic brain injury was 39%. Of the 13 patients with SRSE as a result of anoxic brain injury, SRSE was controlled in 5 (56%). The primary determinant of mortality was family withdrawing care related to the presence of severe medical/neurological diseases.

Pyridoxine deficiency in adult patients with status epilepticus.

An 8-year-old girl treated at our facility for superrefractory status epilepticus was found to have a low pyridoxine level at 5 µg/L. After starting pyridoxine supplementation, improvement in the EEG for a 24-hour period was seen. We decided to look at the pyridoxine levels in adult patients admitted with status epilepticus. We reviewed the records on patients admitted to the neurological ICU for status epilepticus (SE). Eighty-one adult patients were identified with documented pyridoxine levels. For comparison purposes, we looked at pyridoxine levels in outpatients with epilepsy (n=132). Reported normal pyridoxine range is >10 ng/mL. All but six patients admitted for SE had low normal or undetectable pyridoxine levels. A selective pyridoxine deficiency was seen in 94% of patients with status epilepticus (compared to 39.4% in the outpatients) which leads us to believe that there is a relationship between status epilepticus and pyridoxine levels.

Safety & pK of IV loading dose of lacosamide in the ICU.

A restrospective review of patients treated in the ICU for refractory status epilepticus who had received an initial IV loading dose of lacosamide (LCS) was performed. A total of 142 patients were identified. The first 34 patients received 400mg which by weight-based measurement ranged from 2 to 11 mg/kg. Higher mg/kg dosing had been used subsequently with doses up to 13 mg/kg. No patient required reduction in rate or cessation of infusion. Initiation of pressor agents was not needed during the infusion of the loading dose. Postinfusion LCS blood levels were drawn, and dosing of 10-12 mg/kg and higher resulted in blood levels above 15 µg/ml while doses of 2-6 mg/kg resulted in levels below 10 µg/ml. We conclude that a weight-based loading dose of 10-12 mg/kg at an infusion rate of 0.4 mg/kg/min is safe and will produce levels of 15 µg/ml and higher. This article is part of a Special Issue entitled "Status Epilepticus".

Bispectral Index monitoring correlates with sedation scales in brain-injured patients.

OBJECTIVE: Monitoring critically ill, brain-injured patients with a decreased level of consciousness is challenging. Our goal is to determine in this population the correlation between the Bispectral Index (BIS) and three commonly used sedation agitation scales: the Richmond Agitation-Sedation Scale (RASS), the Sedation-Agitation Scale (SAS) and the Glasgow Coma Scale (GCS) scores. DESIGN: Prospective, single-blinded observational study. SETTING: Eight-bed neurology-neurosurgery intensive care unit at the Cleveland Clinic Foundation. PATIENTS: Thirty critically ill patients admitted to the neurointensive care unit with primary brain injury and a decreased level of consciousness. MEASUREMENTS AND MAIN RESULTS: Patients were prospectively evaluated for level of consciousness using the RASS, SAS, and GCS every hour and simultaneously were monitored continuously with a BIS monitor for 6 hrs. A Spearman's correlation coefficient was used to correlate the BIS scores with clinical scales. In 15 patients monitored with the newer BIS XP version, the BIS values correlated significantly with the RASS (R2 = .810; p < .0001), SAS (R2 = .725; p < .0001), and GCS (R2 = .655; p < .0001). In 15 patients monitored with the older BIS 2.1.1 software, the correlation was as follows: for RASS, R2 = .30 (p < .008), for SAS: R2 = .376 (p < .001), and for GCS: R2 = .274 (p < .015). This correlation was maintained in patients who received sedative medications. CONCLUSIONS: A statistically significant correlation existed between BIS values and the RASS, SAS, and GCS scores in critically ill brain-injured patients, with and without sedation. The newer BIS XP software package may be a useful adjunctive tool in objective assessment of level of consciousness in brain-injured patients.

Leukocyte reduction during orthotopic liver transplantation and postoperative outcome: a pilot study.

STUDY OBJECTIVE: To investigate the effect of intraoperative leukocyte reduction of administered blood products on the incidence of acute cellular rejection and postoperative patient outcome. DESIGN: Prospective, nonrandomized, historical control study. SETTING: Academic tertiary medical center. PATIENTS: The study group (Group 1) consisted of 30 consecutive adult patients with end-stage liver disease scheduled to undergo orthotopic liver transplantation (OLT) between 1998 and 2000. The historical control group (Group 2) consisted of 30 adult patients with end-stage liver disease matched to study group patients as closely as possible for age, gender, and etiology of liver disease who underwent OLT between 1995 and 1999. INTERVENTIONS: Group 1 patients had all intraoperative allogeneic and cell salvaged blood products leukocyte reduced before administration. Group 2 patients underwent OLT without leukocyte filtration of any administered blood products. MEASUREMENTS: Demographic data were collected for both patient groups and included age, gender, etiology of liver disease, and both intraoperative and postoperative immunosuppression. Demographic allograft donor data for both patient groups were collected and included age, gender, use of vasopressors during procurement, and cold and warm donor organ ischemic times. Outcome variables measured included incidence of acute cellular rejection, length of intensive care unit (ICU) and length of hospital stay, incidence of both graft loss and retransplantation, and mortality. MAIN RESULTS: The incidence of acute cellular rejection was 40% in Group 1 and 66.7% in Group 2 (p = 0.037). Length of ICU stay was 3.0 (2.0, 5.0) days in Group 1 and 4.0 (3.0, 6.0) days in Group 2 (p = 0.16). Length of hospital stay was 14.0 (11.0, 18.0) days in Group 1 and 18.0 (14.0, 27.0) days in Group 2 (p = 0.035). One allograft was lost in Group 2 because of primary nonfunction requiring retransplantation (p = 0.31), and three postoperative deaths occurred in Group 1 as a result of multisystem organ failure (p = 0.08). CONCLUSIONS: Coincident with leukocyte reduction of all administered blood products during OLT, an improved outcome was observed in Group 1 patients as demonstrated by both a decreased incidence of acute cellular rejection and length of hospital stay.

Use of propofol to control refractory involuntary movements.

The authors report the first case of propofol use for the control of non-epileptic involuntary movements in a patient with postviral encephalitis. The withdrawal from propofol was associated with re-emergence of involuntary movements. The patient was maintained on propofol infusion for 6 months while a series of medications were used in an attempt to control the movements. The movements were finally controlled with high doses of phenobarbital, diazepam, and olanzapine, and the propofol was slowly weaned.