Sharon M. Watling

Prolonged paralysis in intensive care unit patients after the use of neuromuscular blocking agents: a review of the literature.

ObjectivesTo review the reports of prolonged neuromuscular blockade secondary to vecuronium and atracurium administration. To propose mechanisms for prolonged blockade, as well as methods to avoid prolonged blockade. Data SourcesA literature search was conducted of articles published from 1980 to 1993. Articles pertaining to pharmacokinetic and pharmacodynamic alterations, prolonged neuromuscular blockade, and continuous infusion administration of vecuronium and atracurium were obtained. Study SelectionStudies and case reports pertaining to prolonged neuromuscular blockade in intensive care unit patients were reviewed and summarized. Data ExtractionAll articles were reviewed by both authors. Primarily, the critical care literature and anesthesia literature were reviewed. Case reports were divided into two groups, based on end-organ function and possible cause. Data SynthesisProlonged neuromuscular blockade can be divided into two types. One is pharmacokinetically based, due to alterations in clearance and metabolite formation. The second occurs in patients without an etiology for drug clearance problems. Functional neuromuscular junction defects are the problem and may be due to the underlying disease state in addition to, or regardless of, the use of neuromuscular blocking agents. ConclusionsControlled studies assessing the appropriate drug, administration method, use of drug in end-organ dysfunction, and monitoring techniques are unavailable. From the available case reports, length of neuromuscular blockade has been associated with endorgan dysfunction, concomitant drug use, severity of the underlying illness, length of therapy, monitoring techniques used, and perhaps method of drug administration. Steroidally based neuromuscular blocking agents may be particularly hazardous in patients receiving systemic corticosteroids. It is premature to determine the safety of one particular neuromuscular blocking drug in relation to another. Further studies are needed to optimize the use and safety of neuromuscular blocking agents in intensive care unit patients. (Crit Care Med 1994; 22:884–893)

Sedatives, analgesics, and paralytics in the ICU.

Objective To solicit practitioner-perceived opinions regarding current sedative/analgesic/paralytic practice including drug selection, admixture methods, and methods of assessing patient response to therapy via a survey tool; and to assess sedative/pain/paralytic drug use patterns including dosage, route, selection, and combination therapy by collecting actual drug administration data from multiple centers. Methods Respondents completed a survey and collected drug administration data for 5 consecutive days in the intensive care unit (ICU) in which they practiced. Participants One hundred thirty-eight members of the Society of Critical Care Medicine Clinical Pharmacology and Pharmacy section and the Critical Care Practice Research Network of the American College of Clinical Pharmacy agreed to participate in the study. Results Fifty-one percent of the participants completed surveys, and 45% returned drug administration data collection forms. Patients received sedative/pain/paralytic therapy 62% of the 5 days studied. The most frequently received drugs were opiates, followed by benzodiazepines. Intermittent intravenous injection, oral/enteral, and continuous infusion methods were used in most patients. Combination therapy was used 25% of the time, with benzodiazepine/opiate combinations used most often (46%). Administration protocols were rarely used. Paralytic agents were occasionally administered without sedative/pain therapy. Conclusions Patients received these agents during the majority of their ICU stay. Multicenter drug use data suggested a preference for opiate and benzodiazepine therapy. Many centers used continuous infusion therapy despite minimal pharmacokinetic/pharmacodynamic information on ICU patients. Further studies are needed to standardize end points, as well as obtain both pharmacokinetic/pharmacodynamic and stability data in ICU patients.

Aminoglycoside Dosing Considerations in Intensive Care Unit Patients

OBJECTIVE: Factors affecting aminoglycoside dosing requirements in critically ill adult patients were reviewed. DATA SOURCES: A literature search was performed from 1979 to 1992 and articles pertaining to aminoglycoside dosing were obtained. STUDY SELECTION: Only studies appearing in peer-reviewed journals were selected. Topics selected included: Bactericidal kill kinetics, once-daily dosing regimens, critical illness, toxicity, aminoglycosides, intensive care unit, and lung penetration. CONCLUSIONS: Studies suggest that larger initial aminoglycoside doses are necessary in critically ill patients (tobramycin/gentamicin 3 mg/kg or amikacin 9 mg/kg) to achieve adequate peak serum concentrations. Current studies have not shown an increase in the incidence of aminoglycoside toxicity when using these larger initial doses. Follow-up monitoring is dependent upon the patients physiology and risk factors for aminoglycoside-induced toxicity.

Verapamil Overdose: Case Report and Review of the Literature:

OBJECTIVE: To report the presentation and controversies regarding therapy of an 18-year-old man following a life-threatening ingestion of verapamil. CASE SUMMARY: An 18-year-old man ingested large quantities of dipyridamole, trimethoprim/sulfamethoxazole, amoxicillin, and verapamil. He presented to an outlying hospital and was initially conscious. Soon thereafter, the patient had a seizure; he required intubation, developed cardiac conduction abnormalities, and became hypotensive. The patient required pharmacologic pressors and a pacemaker for transfer to our institution. At our institution, vigorous fluid resuscitation, cardiac pacing, and careful attention to acid/base and electrolyte management provided the basis of therapy. The patient recovered without deficit and was discharged from the intensive care unit five days later. DISCUSSION: Current controversies regarding the management of verapamil overdose are reviewed. Removal of the drug by gastric lavage is a mainstay of therapy. Administration of syrup of ipecac is contraindicated. Although specific recommendations for calcium dosing in the overdose situation have not been rigorously studied, maintenance of a normal serum ionized calcium concentration is suggested. An exogenous catecholamine, rather than dopamine, may be the drug of choice for treating hypotension. Cardiopulmonary bypass provides a method for drug removal in cases of severe toxicity; however, this invasive method requires further study. Management of fluid/electrolyte, acid/base, and ventilation abnormalities is required to treat large ingestions of verapamil. Treatment guidelines for critical care clinicians are provided.

A Method to Produce Sedation in Critically Ill Patients

OBJECTIVE: To evaluate a protocol based on continuous infusion of a benzodiazepine and morphine to produce apnea/decreased respiratory effort as an adjunct to complex mechanical ventilation in patients with respiratory failure. DESIGN: Observational report of consecutive patients. SETTING: University medical intensive care unit. PATIENTS: Seventeen consecutive patients with acute respiratory failure requiring high levels of sedation and/or paralysis to facilitate mechanical ventilation were studied. INTERVENTIONS: Patients were started on a continuous infusion of a benzodiazepine and morphine soon after mechanical ventilation was instituted. The dosages of the benzodiazepine and morphine were increased to the end point of diminished respiratory effort or apnea depending on the clinical status of the patient and ventilatory mode. This regimen was supplemented with single doses of neuromuscular blocking agents (NMBAs) only as the dosages of benzodiazepine/narcotic were being titrated. The benzodiazepine/narcotic agents were then gradually reduced as the patients condition improved, often using an oral route of administration. MEASUREMENTS AND RESULTS: The benzodiazepine/morphine combination produced apnea and diminished respiratory effort in patients requiring sedation from 2 to 50 days, including those with hemodynamic instability, hepatic dysfunction, renal dysfunction, and sepsis. The combination allowed the use of NMBAs to be minimized. There was no evidence of worsened hemodynamic instability as a result of the administration of these agents. The gastrointestinal tract could be used for nutrition in 8 of the 17 patients. CONCLUSIONS: Continuous infusion of a benzodiazepine and morphine controlled the respiratory rate in patients with severe respiratory failure requiring complex mechanical ventilatory support.

Population pharmacokinetics: development of a medical intensive care unit-specific gentamicin dosing nomogram.

Objective This study was designed to develop a population-specific dosing nomogram for gentamicin in medical intensive care unit (MICU) patients using the population pharmacokinetic program nonparametric expectation maximization (NPEM). Design Observational clinical gentamicin dosing data were collected, entered into the USC*PACK database program PASTRX, and downloaded into the population pharmacokinetic program NPEM. NPEM generated population pharmacokinetic parameter values that were used to develop a gentamicin dosing nomogram. The nomogram was tested in the next 15 patients admitted to MICU to determine accuracy. Doses given per the MICU and the Hull-Sarubbi nomograms were compared with doses based on actual patient-specific pharmacokinetic parameter values. Reliability coefficients (intraclass correlation coefficients) were calculated to assess the agreement between observations. Setting Data were gathered from patients receiving gentamicin therapy in the MICU, Presbyterian University Hospital, Pittsburgh. Patients Baseline population pharmacokinetic parameter values were determined in 36 MICU patients receiving gentamicin therapy. Patients with renal failure receiving hemodialysis or another mechanical method of blood clearance or fluid removal were excluded. The population parameter values in the form of a dosing nomogram were then used prospectively to dose gentamicin in 15 patients. Results NPEM generated population parameter values similar to those previously published using the Sawchuk-Zaske method in ICU patients. The mean volume of distribution generated using NPEM was 0.34 ± 0.12 L/kg. The relationship between creatinine clearance (Clcr) and elimination rate constant (Ke) was: Ke = 0.00218 x Clcr + 0.007. The nomogram-derived doses correlated with doses determined by using actual patient-specific pharmacokinetic values (p<0.05). The Hull-Sarubbi derived doses, however, did not correlate with patient-specific doses (p>0.05). Only one patient had a peak concentration <6 mg/L. Two of 15 patients had trough concentrations prior to the first maintenance dose >2 mg/L. Conclusions The use of NPEM to generate population-specific pharmacokinetic parameter values has been previously described. Application of population-specific dosing nomograms can improve initial dosing regimens such that conventional therapeutic concentrations can be achieved early in therapy. This nomogram, however, does not preclude follow-up patient-specific pharmacokinetic analysis.

The Impact of Changing Ventilator Parameters on Availability of Nebulized Drugs in an in Vitro Neonatal Lung System

An in vitro model was developed to assess nebulized drug delivery. The model simulated the intubated neonate and examined the effect of changes in a variety of parameters commonly confronted in the clinical setting. Theophylline was nebulized for 15 minutes and captured in an artificial lung system (a 1000-mL intravenous bag). Variables were: Peak pressure (20, 24, 28 cm H2O), ventilator rate (40, 60, 80 breaths/min), nebulizer flow rate (5, 7, 10 L/min), endotracheal tube size (2.5, 3.0, 3.5 mm), and ventilator type (Servo 900C, Bourns BP 200, Bear Cub BP 2001). The amount of drug actually captured in the bag ranged from 0.009 to 12.59 percent (mean 2.08). A multivariate analysis showed that only nebulizer flow rate had a statistically significant effect on drug delivery with 10 L/min delivering the most drug. All factors combined only accounted for 11.5 percent of the variability in drug delivery. In light of the wide and unpredictable amounts of drug delivered through ventilators, dosing to pharmacologic effect rather than staying within narrow dosing guidelines may be more rational in patients responding poorly to standard doses.

Education in the ICU

Little data exists concerning the details of education in the critical care setting. Most of the studies have been done by the nursing profession, examining techniques to improve orientation, continuing education, and methods of teaching. In addition, some newer methodologies have recently been developed that may aid the process, and the roles of other health care professions have increased. This review examines these recent developments and possible ways to exploit their experience to improve critical care education.

Multidisciplinary Approach to Improving Antibiotic Turnaround Time in a Medical Intensive Care Unit

Objective: To improve the timeliness of antibiotic therapy. Setting: A 13-bed university hospital medical intensive care unit. Interventions: Inservice presentations regarding the importance of antibiotic administration time, preprinted antibiotic orders, and a rearrangement of the order processing system were implemented. Results: Overall antibiotic turnaround time decreased from a median of 2.2 hours (March–May 1993) to 1.4 hours (March–May 1994) (p = 0.001). Conclusions: A multidisciplinary team working together developed a system to significantly improve antibiotic turnaround time.