Dennis Parker

Use of sedative and analgesic agents in neurotrauma patients: Effects on cerebral physiology

Abstract Sedation and analgesia is used primarily in the intensive care unit (ICU) to limit the stress response to critical illness, provide anxiolysis, improve ventilatory support, and facilitate adequate ICU care. However, in the neurotrauma ICU there are many other reasons for the use of these agents. The primary aim is to prevent secondary cerebral damage by maintaining adequate cerebral perfusion pressures. This is accomplished in several different ways. Controlling intracranial pressure (ICP) and maintaining an adequate mean arterial pressure (MAP) is at the cornerstone of this management. Lowering the metabolic demands of the brain is also an important consideration as a treatment strategy. Analgesic and sedative agents are utilized to prevent undesirable increases in ICP and to lower cerebral metabolic demands. Concerns surrounding the use of these agents include time to awakening after discontinuation, effect on the cerebrovasculature, and the effect on patient outcome. There are many different pharmacological agents available, each with their distinct advantages and disadvantages. The purpose of this review is to evaluate the pharmacokinetic and pharmacological effects of each of these agents when used in neurotrauma patients. [Neurol Res 2001; 23: 237-259]

Role of hypertonic saline for the management of intracranial hypertension after stroke and traumatic brain injury

Increased intracranial pressure after neurologic injury is a clinical challenge that often requires administration of osmotic agents. The most common osmotic agent used for treatment has been mannitol; however, interest has been renewed in using hypertonic saline after neurologic injury, since it is not associated with hypovolemia. The types of procedures or injury for which hypertonic saline has been used are vast, from elective craniotomy for tumor resection to stroke and traumatic brain injury. Unfortunately, there is a paucity of well‐controlled clinical trials that provide evidence for the best concentration, administration approach, and length of therapy with hypertonic saline. The bulk of the data exists for traumatic brain injury, although most of these data are from observational and retrospective analyses, which do not allow for an evaluation of the impact of hypertonic saline on clinical outcomes. Nonetheless, both animal and clinical data suggest that patients with traumatic brain injury and those with stroke may benefit from hypertonic saline therapy. Since hypertonic saline has a high risk of injury with inappropriate administration and is considered a “high‐alert” drug, safety issues surrounding its dispensing and administration must be considered. Randomized outcome trials comparing mannitol with hypertonic saline in various subpopulations of neurologic injury would add valuable information to the literature and provide a basis for establishment of best clinical practices.

Introducing hypertonic saline for cerebral edema: an academic center experience.

AbstractIntroduction: Use of hypertonic saline (HTS) is gaining acceptance in the neurosciences critical care unit (NCCU) based on its efficacy in reducing cerebral edema and its favorable hemodynamic profile. In the NCCU, unfamiliarity with the use of HTS may result in implementation difficulties. We report our initial experience using HTS, its ability to achieve a hypernatremic state, and adverse effects. Methods: Analysis of 19 consecutive patients who were admitted to the NCCU and treated with 2 or 3% HTS infusion for cerebral edema (target serum sodium: 145–155 mEq/L) included patient diagnoses, laboratory data, length of treatment, adverse effects, and outcome at discharge. We compared the adverse effects of those patients to a contemporary cohort of patients who received mannitol as the sole form of osmotherapy. Results: The HTS cohort had a median age of 46 years (range: 18–70). Median GCS and APACHE II scores were 11 (range: 3–15) and 18 (range: 8–30), respectively. Median length of HTS treatment was 5 days (range: 1–17). Target hypernatremia was achieved in 14 patients (74%), 7 of whom achieved hypernatremia within the first 24 hours. The median number of rescue interventions received for ICP control was 3 (range: 1–30). The adverse effects between the HTS and mannitol cohorts were not found to be significantly different. Conclusion: The use of HTS for cerebral edema requires intensive efforts by the medical team to rapidly achieve and maintain a hypernatremic state. The continuous infusion of HTS was used safely.

Pharmacokinetics of Single-Dose Daptomycin in Patients with Suspected or Confirmed Neurological Infections

ABSTRACT There are currently few or no published data on the amount of cerebrospinal fluid (CSF) penetration of daptomycin in patients with suspected or documented neurosurgical infections. We conducted a prospective study, assessing the pharmacokinetics and CSF penetration of a single intravenous daptomycin dose administered at 10 mg/kg, based on total body weight (TBW), in six neurosurgical patients with indwelling external CSF shunts with suspected or documented meningitis or ventriculitis. Each patient had four blood and CSF samples drawn simultaneously at specific times after the end of infusion: 30 min, 6 h, 12 h, and 24 h. Pharmacokinetic parameters of daptomycin in serum were calculated using standard noncompartmental methods, and daptomycin was assayed using high-performance liquid chromatography (for serum) or liquid chromatography with mass spectrometry (for CSF). The mean (± standard deviation [SD]) maximum measured daptomycin concentrations were 93.7 ± 17.3 mg/liter in serum at 0.5 h postinfusion and 0.461 ± 0.51 mg/liter in CSF at 6 h postinfusion. The mean (± SD) daptomycin minimum concentrations were 13.8 ± 4.8 mg/liter in serum at 24 h postinfusion and 0.126 ± 0.12 mg/liter in CSF at 0.5 h postinfusion. The mean daptomycin penetration, determined by the area under the concentration-time curve in CSF (AUCCSF)/(AUCserum ratio), was 0.8%. Corrected for protein binding, the overall CSF penetration was 11.5%. Additional pharmacokinetic studies evaluating multiple and/or higher dosages of daptomycin are necessary in human subjects to better characterize the CSF penetration of daptomycin in neurosurgical patients.

Considerations in Fluids and Electrolytes After Traumatic Brain Injury

Appropriate fluid management of patients with traumatic brain injury (TBI) presents a challenge for many clinicians. Many of these patients may receive osmotic diuretics for the treatment of increased intracranial pressure or develop sodium disturbances, which act to alter fluid balance. However, establishment of fluid balance is extremely important for improving patient outcomes after neurologic injury. The use of hyperosmolar fluids, such as hypertonic saline, has gained significant interest because they are devoid of dehydrating properties and may have other beneficial properties for patients with TBI. Electrolyte derangements are also common after neurologic injury, with many having neurologic manifestations. In addition, the role of electrolyte abnormalities in the secondary neurologic injury cascade is being delineated and may offer a potential future therapeutic intervention.

Disposition of cefepime in the central nervous system of patients with external ventricular drains.

Study Objective. To assess central nervous system (CNS) penetration of cefepime in adults with external ventricular drains and to compare the achieved cerebrospinal fluid (CSF) concentrations with the usual minimum inhibitory concentrations (MICs) of common pathogens.

Clobazam: An effective add‐on therapy in refractory status epilepticus

Refractory status epilepticus (RSE) is a medical emergency, with significant morbidity and mortality. The use and effectiveness of clobazam, a unique 1,5‐benzodiazepine, in the management of RSE has not been reported before. Over the last 24 months, we identified 17 patients with RSE who were treated with clobazam in our hospital. Eleven of the 17 patients had prior epilepsy. Fifteen patients had focal status epilepticus. Use of clobazam was prompted by a favorable pharmacokinetic profile devoid of drug interactions. Clobazam was introduced after a median duration of 4 days and after a median of three failed antiepileptic drugs. A successful response, defined as termination of RSE within 24 h of administration, without addition or modification of concurrent AED and with successful wean of anesthetic infusions, was seen in 13 patients. Indeterminate response was seen in three patients, whereas clobazam was unsuccessful in one patient. Clobazam averted the need for anesthetic infusions in five patients. Clobazam was well tolerated, and appears to be an effective and promising option as add‐on therapy in RSE. Its efficacy, particularly early in the course of SE, should be further investigated in prospective, randomized trials.

Kidney dysfunction at the time of intracerebral hemorrhage is associated with increased in-hospital mortality: a retrospective observational cohort study

Abstract Objective: Renal dysfunction has been implicated as a risk factor for adverse outcomes after numerous cardiovascular events including stroke. However, most of the stroke studies have focused on long-term results and have primarily examined ischemic stroke. Therefore, we aimed to determine if renal dysfunction was associated with increased initial in-hospital mortality after intracerbral hemorrhage (ICH). Methods: Our retrospective, observational, cohort chart review evaluated the relationship between in-hospital mortality after ICH and renal function, assessed from admission estimated glomerular filtration rate (eGFR), calculated using the abbreviated modification of diet in renal disease equation, in 101 consecutive cases. Results: Survivors had higher admission eGFRs than those who died (88±37 versus 59±33 ml/minute/1·73 m2; P<0·001). Similarly, mortality was higher in patients with eGFR <90 versus those >90 ml/minute/1·73 m2 (40% versus 15%; P = 0·009). Univariate analysis indicated that in-hospital death was associated with intraventricular hemorrhage, ICH volume, age, eGFR <90 ml/minute/1·73 m2, and admission values of serum creatinine, and blood urea nitrogen (P<0·05). Multivariable logistic regression (controlled for confounding variables) revealed that admission eGFR was an independent predictor of death; odds ratio 0·96; 95% confidence interval 0·92–0·99. We also found a negative correlation between eGFR and lesion size (P = 0·041); the lower the eGFR, the larger the lesion. Conclusion: Renal dysfunction was an independent predictor of initial in-hospital mortality after stroke and hence may stratify risk in ICH patients.

Thrombolysis for intraventricular hemorrhage after endovascular aneurysmal coiling

Objective and Importance: Current applications of lytic therapy for intraventricular hemorrhage (IVH) rely on exclusion of vascular abnormalities as etiology. Its use in patients with recently coiled aneurysms remains far from considered safe. We report a patient with subara chnoid hemorrhage (SAH) and massive IVH from aneurysmal rupture, which was safely treated with intraventricular recombinant tissue plasminogen activator (rt-PA) after endovascular coiling. We also review two other similar cases reported in the literature.Clinical Presentation: A 61-year-old man presented with a ruptured anterior communicating artery aneurysm causing SAH and IVH (Hunt & Hess grade IV, Fisher grade III with IVH). During coiling of the aneurysm, extravasation of contrast was noted on fluoroscopy. Follow-up head computed tomography (CT) scan showed casted ventricles. Once in the intensive care unit, the patient progressed to coma, which did not improve with external ventricular drainage alone.Intervention: After endovascular coiling of the aneurysm, intraventricular rt-PA was administered. Isovolemic injections of 2 mg rt-PA every 12 hours were performed for a total of four doses. No clinical or radiological evidence of worsening SAH/IVH was documented. At the time of discharge, the patient was awake but requiring assistance with activities of daily living.Conclusion: We report the safe administration of intraventricular rt-PA after endovascular coiling of a ruptured cerebral aneurysm. Two other similar cases were found in the literature and are reviewed. Hindrance of aneurysmal cavity thrombosis by early administration of rt-PA (increasing the risk of rerupture) remains a widespread concern. The lack of such instances should therefore be acknowledged. We propose that inclusion of such patients in trials assessing safety/efficacy of thrombolytic theray in the treatment of patients with intracranial hemorrhage should be carefully considered.

Neuroleptic Malignant Syndrome Associated with the Use of Prochlorperazine in a Patient with a Recent History of Antipsychotic-Induced Neuroleptic Malignant Syndrome

Objective: To describe a case of neuroleptic malignant syndrome (NMS) associated with the use of prochlorperazine in a patient recently hospitalized for NMS secondary to olanzapine. Case Summary: A 28-year-old African American male with a history of schizophrenia was hospitalized 22 days prior to the current admission for an episode of olanzapine-induced NMS. The patient was discharged from our hospital to an outside psychiatric facility. At this facility, the patient developed nausea and was given 2 doses (unknown amount and route) of prochlorperazine. Over the next 24 hours, the patient exhibited signs and symptoms of NMS including fever, agitation, and muscle rigidity. He was transported to the emergency department and became increasingly agitated. Upon admission, the patient was hyperthermic (rectal temperature 39 °C) and tachycardic (heart rate 138 beats/min), with an elevated white blood cell count of 13.5 × 103/μL, creatine kinase 431 units/L, serum sodium 150 mEq/L, blood urea nitrogen 25 mg/dL, and creatinine 1.1 mg/dL A diagnosis of NMS was speculated and infectious causes were excluded. The patient was treated with aggressive fluid resuscitation and rapid cooling measures, as well as bromocriptine and lorazepam. Cooling measures were used for 48 hours, during which time the creatine kinase, white blood cell count, sodium, blood urea nitrogen, and creatinine gradually normalized. The patient was discharged to a psychiatry facility with a treatment regimen of oxcarbazepine 600 mg twice daily, lorazepam 2 mg 3 times daily, and clozapine 25 mg at bedtime, which was titrated over 2 months to 200 mg twice daity. There have been no further occurrences of NMS. Discussion: The patient had all of the major characteristics of NMS with no other likely causative factors that may have contributed to his illness. Use of the Naranjo probability scale suggested that NMS was probably related to prochlorperazine. This case highlights the potential increased risk with the use of prochlorperazine in a patient with a history of olanzapine-induced NMS. Conclusions: NMS should be considered as a rare complication of therapy with antipsychotics and agents that alter dopamine activity, especially in patients with a history of the syndrome. Careful consideration should be given regarding the risks and benefits of using non-antipsychotic dopamine antagonists in patients with a history of antipsychotic-induced NMS.