Carolina B. Maciel

ICU Management of the Potential Organ Donor: State of the Art

End-organ failure is associated with high mortality and morbidity, in addition to increased health care costs. Organ transplantation is the only definitive treatment that can improve survival and quality of life in such patients; however, due to the persistent mismatch between organ supply and demand, waiting lists continue to grow across the world. Careful intensive care management of the potential organ donor with goal-directed therapy has the potential to optimize organ function and improve donation yield.

Malignant MCA Stroke: an Update on Surgical Decompression and Future Directions

Despite a decline over the past decade in overall stroke mortality, hemispheric strokes retain a strikingly high mortality due to their potential for malignant edema and herniation. The pathogenesis of ischemic cerebral edema is steered by disruption of ionic homeostasis in the neurogliovascular unit. Significant effort has been made to identify potential medical therapies targeting edema formation with promising results. To date, decompressive craniectomy remains the therapy with the most robust impact on mortality. Historically, patient selection for surgical treatment of malignant supratentorial strokes has focused on a strict age cutoff and hemispheric dominance. Recent evidence supports a significant mortality benefit in elderly population, although the impact in morbidity is modest. Careful patient selection for surgical treatment in conjunction with comprehensive neurocritical care and inclusion of family in the educated decision making process remain the mainstay of care for such shattering disease.

Review of the Utility of Prophylactic Anticonvulsant Use in Critically Ill Patients With Intracerebral Hemorrhage

Spontaneous atraumatic intracerebral hemorrhage (sICH) accounts for 10% to 15% of strokes a year and results in significant morbidity and mortality for survivors. The sICH-related, 30-day mortality is 30% to 50% with a significant proportion occurring in the acute phase, often in the first 48 hours,1 which may be a reflection of early withdrawal of life-sustaining therapy based on perceived poor neurological prognosis.2,3 Cerebrovascular disease, including sICH, is the most common cause of acute symptomatic seizures and localization-related epilepsy in adults, accounting for ≈3.2% to 10.7% of epilepsy.4–6 Spontaneous ICH patients typically develop seizures early after their hemorrhage,7–9 but the association between early seizures and late seizures/epilepsy remains uncertain. Our understanding of risk factors for developing seizures and epilepsy, and the role of antiseizure medications in preventing poststroke seizures and epilepsy, is based mainly on retrospective analyses. To date, there are limited data on the impact of seizures, epilepsy, and antiseizure medications on functional and cognitive outcomes in patients with sICH. The goal of this nonsystematic review is to summarize the available literature, focusing on the role of seizure prophylaxis in the immediate and long-term post-sICH periods. To identify key articles for inclusion, MEDLINE on the Ovid platform (through February 14, 2016) and Embase and newer (unindexed/in process) articles from PubMed were searched using the following terms or combination of terms Anticonvulsants, Seizures, Cerebral Hemorrhage, Intracranial Hemorrhage, Nontraumatic, Spontaneous and Critical Care. All identified references were then cross-referenced to select further articles for inclusion. Non-English studies and studies isolated to infants and children were excluded. ### Definitions Seizures occur at various time points after sICH, from onset to weeks, months, and years afterward. Onset or immediate seizures occur either at ictus or within 24 hours of injury and may in fact be …

Seizures and Epileptiform Patterns in SAH and Their Relation to Outcomes.

Summary: In subarachnoid hemorrhage (SAH), seizures are frequent and occur at different time points, likely reflecting heterogeneous pathophysiology. Young patients, those with more severe SAH (by clot burden or presence of severe mental status changes at onset or focal neurologic deficits at any time), those with associated increased cortical irritation (by infarction or presence of underlying hematoma), and patients undergoing craniotomy are at higher risk. Advanced neurophysiologic monitoring allows for seizure burden quantification, identification of subclinical seizures, and interictal patterns as well as neurovascular complications that may have an independent impact on the outcome in this population. Practice regarding seizure prophylaxis varies widely; its institution is often guided by the risk–benefit ratio of seizures and medication side effects. Newer anticonvulsants seem to be equally effective and may have a more favorable profile. However, questions regarding the association of seizures and vasospasm, the therapeutic dosing, timing, and duration of antiepileptic treatment and the impact of seizures and antiepileptics on the outcome remain unanswered. In this review, we provide a broad overview of the work in this area and offer a diagnostic and therapeutic approach based on our own expert opinion.

Ictal-Interictal Continuum: When to Worry About the Continuous Electroencephalography Pattern

Abstract Continuous electroencephalography (cEEG) monitoring is an invaluable tool in the evaluation of encephalopathy and coma in critically ill patients. Marked increases in cEEG monitoring, coinciding with several societal guideline statements in the last decade, have allowed earlier detection and treatment of clearly harmful patterns, including nonconvulsive seizures (NCSz) and nonconvulsive status epilepticus (NCSE). However, it has also unmasked a range of EEG patterns of less clear clinical significance, with some more “malignant” than others given their potential association with increased neuronal stress and secondary brain injury. These patterns lay on a spectrum often referred to as the ictal‐interictal continuum (IIC). To date, no definitive guidelines exist for the management of these potentially harmful EEG patterns, thus presenting a clinical dilemma for critical care physicians. Here, we review the various IIC patterns, their associated features, seizure risk, and outcomes and also propose a clinical approach to management based on the available data and expert opinion.

A spicy status: Synthetic cannabinoid (spice) use and new-onset refractory status epilepticus—A case report and review of the literature:

Synthetic cannabinoids refer to a wide variety of chemicals engineered to bind cannabinoid receptors (CB1 and CB2) and mimic the effects of delta-9-tetrahydrocanabinol. The potential for severe toxicity and limited in vivo data make synthetic cannabinoid intake an important public health and safety concern. Neurologic toxidromes associated with their use include mental status changes, panic attacks, memory distortions, acute psychosis (e.g. paranoia, delusional thoughts), disorganized behavior, and suicidal and homicidal thoughts. Systemic complications include vomiting, sinus tachycardia, myocardial infarction, and acute kidney injury. Seizures are common; however, status epilepticus is not widely reported. In this case report, we describe a patient who developed acute psychosis and new-onset refractory status epilepticus necessitating emergent neurological life-support and prolonged admission to an intensive care unit following abuse of synthetic cannabinoids. We include a brief review of the literature to prepare the treating clinician for the broad clinical spectrum of this increasingly common intoxication.

Clinical Reasoning: Prognostication after cardiac arrest: What do we really know?

A 43-year-old woman with a history of hypertension had a witnessed collapse while smoking crack cocaine. Immediate bystander cardiopulmonary resuscitation was performed for 15 minutes; total downtime was estimated at 30 minutes with return of spontaneous circulation (ROSC) achieved after defibrillation of ventricular fibrillation and a total of 5 mg IV epinephrine. Cardiac catheterization showed normal coronary vasculature. Initial neurologic examination 2 hours after fentanyl and vecuronium boluses was significant for nonreactive pupils, absent gag reflex, and no motor response to noxious stimulation, but intact corneal and oculocephalic reflexes. Head CT (obtained to rule out intracerebral hemorrhage in the setting of cocaine use) showed no acute abnormalities. Targeted temperature management (TTM) was initiated 3 hours after ROSC, targeting 32–34°C, and maintained for 24 hours. Continuous EEG initially showed a discontinuous pattern with widespread attenuation, followed by left temporal lateralized periodic discharges, and then by generalized spike and wave discharges. These EEG changes occurred during hypothermia and did not have any clinical correlate. The patient was treated with levetiracetam 55 mg/kg/d with improvement in hyperexcitable patterns. Ten hours after achieving normothermia, she developed frequent myoclonic jerking of her lower extremities, time-locked with epileptiform bursts, consistent with myoclonic status epilepticus (MSE) (figure 1A). Neurologic examination 48 hours after rewarming was unchanged, except for the development of 1–3 Hz myoclonic blinking and jerking of the upper and lower extremities.

Organ donation protocols

Organ transplantation improves survival and quality of life in patients with end-organ failure. Waiting lists continue to grow across the world despite remarkable advances in the transplantation process, from the creation of public engagement campaigns to the development of critical pathways for the timely identification, referral, approach, and treatment of the potential organ donor. The pathophysiology of dying triggers systemic changes that are intimately related to organ viability. The intensive care management of the potential organ donor optimizes organ function and improves the donation yield, representing a significant step in reducing the mismatch between organ supply and demand. Different beliefs and cultures reflect diverse legislations and donation practices amongst different countries, creating a challenge to standardized practices. Maintaining public trust is necessary for continued progress in organ donation and transplantation, hence the urge for a joint effort in creating uniform protocols that ensure transparent practices within the medical community.

Cerebral Edema After Cardiac Arrest: Tell Tale Sign of Catastrophic Injury or a Treatable Complication?

Despite advances in cardiopulmonary resuscitation (CPR) for cardiac arrest being proposed as early as the 1950s [1] and 1960s [2], only in the modern era has the use of specific interventions such as post-arrest therapeutic hypothermia [3] and community-wide emergency medical services, like bystander-initiated CPR and first responder defibrillation [4], consistently demonstrated a benefit to survival. In addition, a recent Cochrane review has determined that the only strategy that has shown improvement in neurologic outcome after cardiac arrest is induction of mild therapeutic hypothermia [5]. Diffuse brain edema early after cardiac arrest is often associated with a dismal neurological examination and poor outcomes, and the use of osmotic agents has not been shown to reverse or improve either. Clear guidance on how to manage cerebral edema post-cardiac arrest has not been established, and efforts in this regard may possibly be futile. Intensivists from prior generations presciently anticipated a need for brain-oriented resuscitative measures and therapies [6]. However, the pathophysiologic mechanisms of cardiac arrest associated with secondary inflammatory and hormonal responses, during and after resuscitation [also known as post-cardiac arrest syndrome (PACS)] [7], and with secondary brain injury like cerebral edema formation have only recently been established from a molecular biologic basis. More recently, water transport channels, such as Aquaporin-4 (AQP4) [8] and Sur1Trmp4 [9], are now being evaluated as potential secondary targets for inhibiting cerebral edema formation after cardiac arrest. The mechanisms of cardiac arrest-induced cerebral edema formation are likely multifactorial; however, one main mechanism thought to be related is the perivascular pool of AQP4, which is rate limiting for water influx during cerebral edema formation and the site of action for osmotic agents that cause brain water efflux [10]. Although it has been known for two decades that the perivascular pool of AQP4 localizes to the astrocyte endfeet adjacent to the blood–brain barrier, progress in the identification of smallmolecule aquaporin inhibitors has been exceedingly slow [11]. In this issue of Neurocritical Care, Nakayama et al. [10] report their results on attenuating cerebral edema and blood–brain barrier disruption after successful resuscitation from an 8-min arrest induced with intravenous potassium chloride in a mouse model. In their series of well-designed experiments, they found that a continuous intravenous infusion of conivaptan, a V1a and V2 antagonist, targeting a serum osmolality goal of approximately 350 mOsm/L, attenuates regional brain edema development, particularly in the caudo-putamen complex and cortex via the perivascular AQP4 pool (areas where the perivascular pool of AQP4 is more prevalent). The novel use of intravenous conivaptan, a dual arginine vasopressin (AVP) receptor antagonist, is thought to be mediated through its antagonism on V1a receptors in the brain via interactions with AQP4, and on V2 receptors by downregulating AQP2 channel expression in the kidney, which can induce diuresis. The efficacy of water efflux requires maintaining a & David M. Greer david.greer@yale.edu

American neuroborreliosis presenting as cranial polyneuritis and radiculoneuritis

Lyme disease is a tickborne illness caused primarily by Borrelia burgdorferi in the United States. CNS involvement typically manifests as 1 or a combination of 3 classic syndromes: meningitis, radiculoneuritis, and cranial neuritis. While facial nerve involvement represents about 80% of cranial neuritis in Lyme neuroborreliosis (LNB), other cranial nerves may also be individually involved; however, multiple cranial nerve involvement is unusual. We report a case of LNB with simultaneous involvement of the third, fifth, sixth, and seventh cranial nerves in addition to cervical and thoracic radiculoneuritis.