Denise H. Rhoney

National Survey of the Use of Sedating Drugs, Neuromuscular Blocking Agents, and Reversal Agents in the Intensive Care Unit

The objectives of this study were to describe the sedative, neuromuscular blocking agents (NMBA) and reversal agents utilized in adult intensive care units across the United States and determine the adherence to American College of Critical Care Medicine and Society of Critical Care Medicine (SCCM) guidelines. In addition, the authors assessed the use of written protocols, criteria used for selecting these agents, and monitoring practices. Questionnaires were mailed to attending physician members of SCCM in the spring of 1998. A cover letter was enclosed that explained the purpose of the survey asking the respondent to forward the questionnaire to a colleague if unable to complete. Four-hundred fifty-seven questionnaires were returned representing 393 different institutions for a response rate of 50.4% (393/780). Respondents were physicians (91.2%) practicing in a community (49.7%) or university teaching hospital (38.3%). The sedative agents used most often were opioids and benzodiazepines for > 72 hours, and NMBA utilized were vecuronium and pancuronium for > 24 hours. The most often cited indications for sedatives were agitation, anxiety/fear, and facilitation of intubation and maintenance of mechanical ventilation for NMBA. Only 32.6% used written protocols for sedatives and 46.8% for NMBA. Decisions regarding agent selection were based on clinician preference and experience and agent duration of action. Seventy-eight percent monitored sedative use primarily with the Glasgow Coma Scale and the modified Ramsay score. Monitoring of NMBA was used more frequently (91.3%) with peripheral nerve stimulation. The most common reversal agents used were naloxone and flumazenil for adverse drug effects. While many of the respondents indicated they used morphine and lorazepam for long-term sedation, the majority utilized midazolam and propofol for > 24 hours despite the recommendation of SCCM. Vecuronium was prescribed more routinely than pancuronium. The number of institutions utilizing protocols for any of these agents was low; instead, decisions were based on clinician preference.

Low-Dose Recombinant Tissue-Type Plasminogen Activator Enhances Clot Resolution in Brain Hemorrhage: The Intraventricular Hemorrhage Thrombolysis Trial

Background and Purpose— Patients with intracerebral hemorrhage and intraventricular hemorrhage have a reported mortality of 50% to 80%. We evaluated a clot lytic treatment strategy for these patients in terms of mortality, ventricular infection, and bleeding safety events, and for its effect on the rate of intraventricular clot lysis. Methods— Forty-eight patients were enrolled at 14 centers and randomized to treatment with 3 mg recombinant tissue-type plasminogen activator (rtPA) or placebo. Demographic characteristics, severity factors, safety outcomes (mortality, infection, bleeding), and clot resolution rates were compared in the 2 groups. Results— Severity factors, including admission Glasgow Coma Scale, intracerebral hemorrhage volume, intraventricular hemorrhage volume, and blood pressure were evenly distributed, as were adverse events, except for an increased frequency of respiratory system events in the placebo-treated group. Neither intracranial pressure nor cerebral perfusion pressure differed substantially between treatment groups on presentation, with external ventricular device closure, or during the active treatment phase. Frequency of death and ventriculitis was substantially lower than expected and bleeding events remained below the prespecified threshold for mortality (18% rtPA; 23% placebo), ventriculitis (8% rtPA; 9% placebo), symptomatic bleeding (23% rtPA; 5% placebo, which approached statistical significance; P=0.1). The median duration of dosing was 7.5 days for rtPA and 12 days for placebo. There was a significant beneficial effect of rtPA on rate of clot resolution. Conclusions— Low-dose rtPA for the treatment of intracerebral hemorrhage with intraventricular hemorrhage has an acceptable safety profile compared to placebo and historical controls. Data from a well-designed phase III clinical trial, such as CLEAR III, will be needed to fully evaluate this treatment. Clinical Trial Registration— Participant enrollment began before July 1, 2005.

Infection related to intracranial pressure monitors in adults: analysis of risk factors and antibiotic prophylaxis

OBJECTIVE Infection is a complication related to intracranial pressure monitoring devices. The timing, duration, and role of prophylactic antimicrobial agents against intracranial pressure monitor (ICPM) related infection have not previously been well defined. Risk factors and selection, duration, and timing of antibiotic prophylaxis in patients with ICPMs were evaluated. METHODS Records of all consecutive patients who underwent ICPM insertion between 1993 and 1996 were reviewed. Patients included were older than 12 years with an ICPM placed for at least 24 hours. Exclusion criteria consisted of ICPM placed before admission or documented CSF infection before or at the time of insertion. Standard criteria were applied to all patients for diagnosis of CSF infection. RESULTS A total of 215 patients were included, 16 (7.4%) of whom developed CSF infection. Antibiotic prophylaxis for ICPM placement was administered to 63% of infected and 59% of non-infected patients. Vancomycin (60%) and cefazolin (34%) were used most often. Sixty per cent (6/16) of patients who developed infection and 45% (53/199) of those without CSF infection received their first antibiotic dose within the 2 hours before ICPM insertion. Risk factors for CSF infection included duration of monitoring greater than 5 days (RR 4.0 (1.3–11.9)); presence of ventriculostomy (RR 3.4 (1.0–10.7)); CSF leak (RR 6.3 (1.5–27.4)); concurrent systemic infection (RR 3.4 (1.2–9.5)); or serial ICPM (RR 4.9 (1.7–13.8)). CONCLUSIONS Administration of antibiotics to patients before or at the time of ICPM placement did not decrease the incidence of CSF infection. Patients found to be at greater risk for infection at our institution included duration of ICPM greater than 5 days, use of ventricular catheter, CSF leak, concurrent systemic infection, or serial ICPM.

Safety and feasibility of continuous infusion of remifentanil in the neurosurgical intensive care unit.

OBJECTIVE Remifentanil is a selective mu-opioid agonist with a context-sensitive half-time of 3 to 5 minutes, independent of dose or administration duration. Other desirable effects include decreased cerebral metabolism and intracranial pressure (ICP) with minimal cerebral perfusion pressure changes. We present six cases illustrating indications for the use of remifentanil in the neurosurgical intensive care unit. METHODS Patients received bolus doses of remifentanil of 0.05 to 1.0 microg/kg, followed by continuous infusions of 0.03 to 0.26 microg/kg/min, titrated to effect. When infusions were discontinued for neurological examinations, another bolus dose preceded infusion reinstitution. Indications for the use of remifentanil included mean arterial pressure and cerebral perfusion pressure decreases with the use of other agents (e.g., codeine or propofol) for ICP control, elevated ICP that was refractory to propofol/mannitol treatment, agitation that was unresponsive to standard therapies, and coughing that caused ICP increases after subarachnoid hemorrhage. RESULTS Three patients experienced spontaneous intracranial bleeding (two cases of subarachnoid hemorrhage and one case of intraventricular hemorrhage), and three patients exhibited severe traumatic subdural hemorrhage. All patients recovered from the effects of remifentanil within 3 minutes after discontinuation of infusion, which allowed frequent rapid neurological assessments. Procedures for pulmonary toilet (i.e., endotracheal suctioning, postural drainage, and bronchoscopy) were performed without deleterious ICP increases or mean arterial pressure or cerebral perfusion pressure decreases during remifentanil infusions. CONCLUSION The ultrashort duration of action of remifentanil allowed easy performance of frequent neurological examinations in the neurosurgical intensive care unit. No patient experienced deleterious hemodynamic or neurological effects as a result of remifentanil use.

Intravenous therapy for hypertensive emergencies, part 1

PURPOSE Intravenous antihypertensive agents for the treatment of hypertensive emergencies are reviewed. SUMMARY An estimated 500,000 people in the United States experience a hypertensive crisis annually. Hypertensive emergency is associated with significant morbidity in the form of end-organ damage. Rapid controlled reduction of blood pressure (BP) may be necessary to prevent or minimize end-organ damage. I.V. antihypertensive agents available for the treatment of hypertensive emergencies are, in general, characterized by a short onset and offset of action and predictable responses during dosage adjustments to reach BP goals, without excessive adjustment or extreme fluctuations in BP. Nicardipine, nitroprusside, fenoldopam, nitroglycerin, enalaprilat, hydralazine, labetalol, esmolol, and phentolamine are i.v. antihypertensive agents recommended for use in hypertensive emergency by the seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Since the publication of these recommendations, another i.v. antihypertensive agent, clevidipine, became commercially available. The selection of a specific agent should be based on the agents pharmacology and patient-specific factors, such as comorbidity and the presence of end-organ damage. CONCLUSION The rapid recognition and initiation of therapy are key to minimizing end-organ damage in patients with hypertensive emergency. Tailoring drug selection according to individual patient characteristics can optimize the management and potential outcomes of patients with hypertensive emergency.

A Review of Stress Ulcer Prophylaxis in the neurosurgical intensive care unit

STRESS ULCERS OCCUR frequently in intensive care unit patients who have intracranial disease. After major physiological stress, endoscopic evidence of mucosal lesions of the gastrointestinal tract appears within 24 hours of injury; 17% of these erosions progress to clinically significant bleeding. Gastrointestinal hemorrhage has been associated with mortality rates of up to 50%. The pathogenesis of stress ulcers may not be completely understood, but gastric acid and pepsin appear to play significant roles. Antacids, H2 antagonists, and sucralfate are effective prophylactic agents in the medical/surgical intensive care unit. Appropriate therapy for neurosurgical patients remains unclear, however. This review summarizes the current literature regarding the pathogenesis and therapy of stress ulcers in neurosurgical patients.

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]

National survey on the use of sedatives and neuromuscular blocking agents in the pediatric intensive care unit.

Objectives To describe the sedative and neuromuscular blocking agents (NMBA) that are currently used in pediatric intensive care units across the country and to assess the use of written protocols for their use, criteria used for selecting these agents, monitoring practices, and clinicians responsible for making therapeutic decisions in the pediatric intensive care units. Design A questionnaire was mailed to pediatric attending physician members of the Society of Critical Care Medicine practicing in the United States in January 1997. A cover letter was also enclosed that explained the purpose of the survey and asked the respondent to forward the questionnaire to a colleague if unable to complete. Results A total of 176 questionnaires were returned, which represented 145 pediatric institutions across the country, for a response rate of 51%. The agents reported to be used most often for sedation were the opioids and benzodiazepines, which were used for >72 hrs. The NMBA used were vecuronium and pancuronium, which were used for >48 hrs. Newer agents such as propofol and cisatracurium were being used by some clinicians as well. Respondents primarily use the intravenous route of administration as either intermittent bolus or continuous infusion. Frequently cited indications for sedatives were anxiety, fear, and amnesia and facilitation of intubation and maintenance of mechanical ventilation for NMBA. Only 13.4% indicated using written protocols for sedatives and 26.1% for NMBA. Decisions regarding the choice of agent were usually based on clinician preference and experience and the duration of action of the agent. Respondents most often reported using clinical assessment (57%) or the Glasgow Coma Scale (47.3%) to monitor the depth or adequacy of sedation. Over 80% of those surveyed use a peripheral nerve stimulator to monitor NMBA activity. Conclusion Clinicians continue to use the opioids and benzodiazepines most often for sedation in the pediatric intensive care units, but newer agents are being used more often and warrant further investigation. The use of written protocols is very low, possibly because of the lack of guidelines in the literature on pediatric intensive care unit sedation and neuromuscular blockade. Development and implementation of protocols for the selection, use, and monitoring of sedatives and NMBA through a multidisciplinary team approach may be a beneficial way to provide safe and cost-effective therapy to critically ill pediatric patients.

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.

Indomethacin: a review of its cerebral blood flow effects and potential use for controlling intracranial pressure in traumatic brain injury patients.

Traumatic brain injury (TBI) causes about 75,000 deaths and leaves approximately 200,000 people disabled in USA each year. Brain swelling and increased intracranial pressure (ICP) contribute to this morbidity and mortality. Aggressive management protocols, including ICP control, have been shown to reduce the overall mortality from 50% to 36% following severe head injury. Despite these encouraging results, new and improved pharmacologic strategies to control ICP are required. Indomethacin (IND) is a non-steroidal anti-inflammatory agent with unique effects on cerebral blood flow physiology which may be of benefit in reducing elevated ICP in TBI patients. Data from animal models and randomized, controlled studies with pre-term infants have shown that i.v. IND produces rapid, significant reductions in cerebral blood flow (CBF). Controlled studies of i.v. IND in normal volunteers show a reduction in CBF from 26%-40%. Case series involving severe TBI patients suggest that IND i.v. boluses of 30-50 mg reduce ICP by 37%-52%, reduce CBF by 22%-26%, with a modest 14% increase in cerebral perfusion pressure (CPP). Despite these encouraging results, i.v. IND should only be considered an experimental treatment for control of refractory ICP in TBI patients. Larger, well-designed randomized trials in TBI patients will provide more efficacy and safety data and delineate the effects of IND alone or in combination with other proven, effective, or experimental therapies. Once these concerns have been addressed, larger outcome studies will ultimately be needed to determine the role of IND for ICP control in TBI patients.