Search PubMed⌕ Search

Biomedical subjects

B J Zarowitz

Publications and source records attributed to B J Zarowitz.

At least 19 recordsLinked to original sources
PubMed2001

Managing the pharmaceutical industry-health system interface.

BACKGROUND: Direct-to-consumer advertising, media, and Internet marketing to physicians and patients, as well as enticing marketing strategies, are used by the pharmaceutical industry to ensure market share growth of new drugs. Our health system adopted a strict vendor policy governing detailing and sampling activities of pharmaceutical representatives, but realized that further analysis of vendor influence in our system was needed. OBJECTIVE: An assessment of tangible benefits, ethical concerns, and financial liabilities and gains was conducted to reassess the need for further vendor restriction. CONCLUSIONS: Based on our findings, several recommendations have been made. Medical practices and health systems are encouraged to establish and enforce explicit vendor policies, measure their effectiveness, partner proactively with representatives to deliver a drug-detailing message consistent with system initiatives, monitor and regulate continuing medical education funding, and implement strategies to ensure appropriate drug use.

Advertising↗
PubMed2000

Pharmacists' understanding of patient education on metered-dose inhaler technique.

OBJECTIVE: To assess pharmacists' attitudes, beliefs, and knowledge about assessing and educating patients regarding metered-dose inhaler (MDI) technique; to determine frequency of MDI assessment and teaching behavior; and to assess the effect of an asthma pharmaceutical care educational program on the same variables six months later. DESIGN: Questionnaire completed before and six months after the educational intervention. SETTING: Pharmacies based in clinics owned by a healthcare system located in communities of a large metropolitan area. MAIN OUTCOMES MEASURES: Pharmacists' self-reported frequency of assessment and education; attitudes and beliefs about assessing and educating patients using MDIs; and knowledge of MDI technique. RESULTS: The survey response rate was 53.7% (n = 39) for baseline and 43% (n = 32) for follow-up. Most pharmacists (85.4% at baseline, 87.5% at follow-up; p = 0.79) indicated that they educate patients receiving new MDI prescriptions. In addition, 47.4% at baseline and 68.8% at follow-up indicated they educate patients using inhalers for three months (p = 0.07). Only 21.1% at baseline and 18.8% at follow-up (p = 0.81) indicated that they follow up with long-term users. The mean +/- SD MDI technique knowledge score (steps correct out of 9 possible) at baseline was 7.2 +/- 1.1 and 7.5 +/- 1.3 at follow-up (p = 0.29). Significant changes in level of agreement with some beliefs/attitudes were observed, including the importance of frequently assessing/educating patients, confidence and comfort when assessing/educating patients, and that assessing/educating patients is not the role of only the physician. Respondents continued to acknowledge that MDI education and assessment are important to improving and maintaining control of disease. However, the respondents thought that barriers exist that inhibit this activity, such as not enough time for education and assessment. CONCLUSIONS: Pharmacists reported they frequently educate patients and assess MDI technique for new prescriptions but not very often for patients recently started, as well as for long-term users. Six months after an educational program, attitudes and beliefs toward this activity were either not changed or, in some, improved. Pharmacists perceive that there is not enough time to assess and educate patients who use MDIs.

Adult↗
PubMed1999

Single versus multiple doses of acetazolamide for metabolic alkalosis in critically ill medical patients: a randomized, double-blind trial.

OBJECTIVE: To compare two dosing regimens of acetazolamide for the reversal of metabolic alkalosis in mechanically ventilated patients with asthma or chronic obstructive pulmonary disease. DESIGN: A randomized, double-blind, placebo-controlled trial. SETTING: A 35-bed medical intensive care unit in a tertiary care teaching hospital. PATIENTS: Forty mechanically ventilated patients with a metabolic alkalosis (arterial pH > or = 7.48 and serum bicarbonate concentration > or = 26 mEq/L) resistant to fluid or potassium therapy (serum potassium concentration, > or = 4 mEq/L) not receiving acetazolamide or sodium bicarbonate in the previous 72 hrs. INTERVENTIONS: Stratified by previous diuretic use and randomized to receive intravenous administration of acetazolamide, one dose of 500 mg or 250 mg every 6 hrs for a total of four doses. MEASUREMENTS AND MAIN RESULTS: Serum bicarbonate and potassium concentrations were drawn every 6 hrs for 72 hrs, arterial blood gases were drawn every 12 hrs for 72 hrs, and both urine chloride and pH were drawn at hours 0, 6, 12, 18, 24, 48, and 72. By using generalized estimating equation techniques, no difference was found between the two dosing regimens at any point over the study period for serum bicarbonate, serum potassium, or urine chloride end points. Results did not differ between diuretic- and nondiuretic-treated patients. Serum bicarbonate concentrations remained significantly decreased in both treatment groups 72 hrs after administration of the first acetazolamide dose (31.8 +/- 4.9-25.3 +/- 3.8 mEq/L, p < .0001 [250 mg x 4]; 31.9 +/- 25.4-25.4 +/- 3.6 mEq/L, p < .0001 [500 mg x 1]). CONCLUSIONS: We conclude that a single 500-mg dose of acetazolamide reverses nonchloride responsive metabolic alkaloses in medical intensive care unit patients as effectively as multiple doses of 250 mg. Studies to examine the prolonged duration of action of acetazolamide observed in this study as well as the effect of acetazolamide on clinical end points, such as duration of mechanical ventilation, are warranted.

Acetazolamide↗
PubMed1999

Motor Activity Assessment Scale: a valid and reliable sedation scale for use with mechanically ventilated patients in an adult surgical intensive care unit.

OBJECTIVE: To establish the validity and reliability of a new sedation scale, the Motor Activity Assessment Scale (MAAS). DESIGN: Prospective, psychometric evaluation. SETTING: Sixteen-bed surgical intensive care unit (SICU) of a 937-bed tertiary care, university-affiliated teaching hospital. PATIENTS: Twenty-five randomly selected, adult, mechanically ventilated, nonneurosurgical patients who were admitted to the SICU > or = 12 hrs after surgery and were not receiving neuromuscular blockers. INTERVENTION: Four hundred assessments (eight per patient) were completed consecutively but independently, in pairs, at standardized times (both day and night) by two nurses who were preselected for each assessment from a pool of 32 pretrained SICU nurses. MEASUREMENTS AND MAIN RESULTS: To estimate validity, paired assessments (four/patient) compared the MAAS result with the subjective assessment using a 10-cm visual analog sedation scale, the percent change in blood pressure and heart rate from the previous 4-hr baselines, and the number of recent agitation-related sequelae. To estimate reliability, paired assessments (four/patient) measured correlation between assessments of the same type (e.g., MAAS-MAAS). Generalized estimating equations, which accounted for the four repeated measures in each patient, supported MAAS validity by finding a linear trend between MAAS and the visual analog scale (p < .001), blood pressure (p < .001), heart rate (p < .001), and agitation-related sequelae (p < .001) end points. The MAAS (kappa = 0.83 [95% confidence interval, 0.72 to 0.94]) was found to be more reliable than subjective assessment using the visual analog scale (intraclass correlation coefficient = 0.32 [95% confidence interval, 0.05 to 0.55]). CONCLUSIONS: The MAAS is a valid and reliable sedation scale for use with mechanically ventilated patients in the SICU. Further studies are warranted regarding the effect of MAAS implementation in our SICU on patient outcomes, such as quality of sedation and length of mechanical ventilation, as well as the use of the MAAS in other patient populations (e.g., medical).

Adult↗
PubMed1998

A primer on continuous renal replacement therapy for critically ill patients.

OBJECTIVES: To characterize the multiple continuous renal replacement therapy (CRRT) techniques available for the management of critically ill adults, and to review the indications for and complications of use, principles of drug removal during CRRT, drug dosage individualization guidelines, and the influence of CRRT on patient outcomes. DATA SOURCES: MEDLINE (January 1981-December 1996) was searched for appropriate publications by using terms such as hemofiltration, ultrafiltration, hemodialysis, hemodiafiltration, medications, and pharmacokinetics; selected articles were cross-referenced. STUDY SELECTION: References selected were those considered to enhance the reader's knowledge of the principles of CRRT, and to provide adequate therapies on drug disposition. DATA SYNTHESIS: CRRTs use filtration/convection and in some cases diffusion to treat hemodynamically unstable patients with fluid overload and/or acute renal failure. Recent data suggest that positive outcomes may also be attained in patients with other medical conditions such as septic shock, multiple organ dysfunction syndrome, and hepatic failure. Age, ventilator support, inotropic support, reduced urine volume, and elevated serum bilirubin concentrations have been associated with poor outcomes. Complications associated with CRRT include bleeding due to excessive anticoagulation and line disconnections, fluid and electrolyte imbalance, and filter and venous clotting. CRRT can complicate the medication regimens of patients for whom it is important to maintain drug plasma concentrations within a narrow therapeutic range. Since the physicochemical characteristics of a drug and procedure-specific factors can alter drug removal, a thorough assessment of all factors needs to be considered before dosage regimens are revised. In addition, an algorithm for drug dosing considerations based on drug and CRRT characteristics, as well as standard pharmacokinetic equations, is proposed. CONCLUSIONS: The use of CRRT has expanded to encompass the treatment of disease states other than just acute renal failure. Since there is great variability among treatment centers, it is premature to conclude that there is enhanced survival in CRRT-treated patients compared with those who received conventional hemodialysis. This primer may help clinicians understand the need to individualize these therapies and to prospectively optimize the pharmacotherapy of their patients receiving CRRT.

Acute Disease↗
PubMed1998

Stress ulcer prophylaxis in medical ICU patients: annual utilization in relation to the incidence of endoscopically proven stress ulceration.

OBJECTIVE: To measure changes in the proportion of medical intensive care unit (MICU) patients prescribed pharmacologic stress ulcer prophylaxis therapy over a 4-year period in relation to the incidence of stress-related ulceration detected by endoscopy at our institution. DESIGN: Retrospective 4-year review of pharmacy and endoscopy databases. SETTING: A 35-bed MICU. PATIENTS: Patients (n = 2941) admitted to the MICU for longer than 24 hours, between January 1, 1993, and December 31, 1996, without acute gastrointestinal hemorrhage on admission. METHODS: Records were reviewed to identify patients prescribed pharmacologic stress ulcer prophylaxis (> 24 h of sucralfate or a histamine2-receptor antagonist [H2RA]), and patients with evidence of stress ulceration during endoscopy. RESULTS: The number of patients per year receiving stress ulcer prophylaxis significantly (p < 0.001) decreased between 1993 and 1996: 1993, 492/693 (71%); 1994, 478/798 (60%); 1995, 295/670 (44%); 1996, 164/780 (21%). There was no difference between years in the median duration of stress ulcer prophylaxis therapy or the proportion of patients receiving sucralfate versus H2RA therapy. There was no difference (p = 0.91) between years in the annual incidence of definite or possible stress-related ulceration: 1993, 6/693 (0.87%); 1994, 5/798 (0.63%); 1995, 6/670 (0.90%); 1996, 5/780 (0.64%). CONCLUSIONS: The incidence of endoscopically proven stress-related ulceration has remained unchanged over the past 4 years in our MICU despite significantly fewer patients receiving pharmacologic stress ulcer prophylaxis therapy.

Anti-Ulcer Agents↗
PubMed1997

A prospective, randomized, controlled evaluation of peripheral nerve stimulation versus standard clinical dosing of neuromuscular blocking agents in critically ill patients.

OBJECTIVES: To determine if vecuronium doses individualized by peripheral nerve stimulation are lower than those doses chosen by standard clinical techniques; and to determine whether patients monitored by peripheral nerve stimulation exhibit shorter recovery times and less prolonged neuromuscular blockade after discontinuation of vecuronium than control patients. DESIGN: A prospective, randomized, controlled, single-blind trial. SETTING: Two ten-bed medical intensive care units of a 937-bed tertiary care, not-for-profit, teaching hospital and health system. PATIENTS: Mechanically ventilated patients requiring continuous neuromuscular blockade as part of their therapy. INTERVENTIONS: After obtaining written, informed consent and baseline neurologic examinations, patients were randomized to treatment, where dosing was individualized by peripheral nerve stimulation or standard clinical assessment. Doses in the peripheral nerve stimulation group were adjusted to 90% blockade (Train-of-Four of 1/4). The standard clinical dosing group received doses individualized to clinical response by the medical team (blinded to Train-of-Four). Differences between groups were evaluated by Wilcoxon matched-pairs signed rank test. MEASUREMENTS AND MAIN RESULTS: A total of 77 patients (35 standard clinical patients vs. 42 peripheral nerve stimulation patients) were enrolled in the study. Despite no difference in initial doses and time to reach 90% blockade or clinical response between groups, the peripheral nerve stimulation group used less drug than the standard clinical group (0.040 +/- 0.028 vs. 0.070 +/- 0.030 mg/kg/hr, respectively, p = .001). The total cumulative amount of vecuronium for the episode of paralysis was greater in the control group (285.8 +/- 246.6 vs. 137.1 +/- 106.4 mg, p = .001). The peripheral nerve stimulation group recovered neuromuscular function (relative risk of 1.85, with 95% confidence interval [CI] of 1.02-3.35, p = .039) and spontaneous ventilation (relative risk of 1.86, 95% CI 1.00-3.45, p = .047) faster than the control group. In patients, adjusting for renal dysfunction, the likelihood of a faster recovery in the peripheral nerve stimulation group increased for neuromuscular function (relative risk of 1.89, 95% CI of 1.07-3.32, p = .018) and spontaneous ventilation (relative risk of 2.27, 95% CI of 1.23-4.21, p = .019). Patients with combined renal and liver failure similarly demonstrated a faster recovery in the peripheral nerve stimulation group. The recovery was affected to a lesser extent by adjusting for concurrent aminoglycoside and corticosteroid administration. CONCLUSIONS: Use of peripheral nerve stimulation for monitoring the degree of blockade and adjusting drug doses in continuously paralyzed critically ill medical patients results in lower doses of vecuronium to maintain a desired depth of paralysis, and allows a faster recovery of neuromuscular function and spontaneous ventilation.

Adult↗
PubMed1996

Disposition of procainamide in patients with chronic congestive heart failure receiving medical therapy.

Dosage reduction of procainamide has been recommended in patients with congestive heart failure (CHF). However, these recommendations are based primarily on studies with unmatched control groups, suboptimal blood sampling, and in patients not receiving angiotensin-converting enzyme (ACE) inhibitors. These agents increase renal blood flow, which theoretically may offset alterations in drug disposition in patients with CHF. The pharmacokinetics of procainamide in patients with chronic CHF and in matched controls were compared. A single intravenous dose of 750 mg of procainamide was administered to 9 patients with chronic New York Heart Association (NYHA) class II or III CHF (mean +/- SD left ventricular ejection fraction 22 +/- 9%) receiving medical therapy and 7 control subjects matched for age and gender. Blood and urine samples were collected at intervals over a period of 48 and 72 hours, respectively. Patients with CHF and control subjects were demographically similar, with the exception of concomitant medications, including ACE inhibitors (8/9 versus 1/7, respectively). There were no significant differences between patients with CHF and control subjects in mean +/- SD peak serum concentrations (Cmax), area under the serum concentration-time curve (AUC0-infinity), total clearance, renal clearance, half-life (t1/2), or volume of distribution (Vd) of procainamide. Similarly, there were no significant differences between patients with CHF and control subjects in the mean +/- SD Cmax, AUC0-infinity, renal clearance, or t1/2 of N-acetylprocainamide (NAPA). Procainamide dosage reduction may not be necessary in patients with chronic stable CHF who are receiving medical therapy.

Adult↗
PubMed1996

Bioelectrical impedance analysis measurements for drug pharmacokinetics.

I review the rationale, methods, and existing data for using bioelectrical impedance to determine drug pharmacokinetics. Because drugs distribute into body compartments after absorption, it is expected that bioelectrical impedance measurements may correlate with drug pharmacokinetics (absorption, distribution, metabolism, and excretion). Authors have examined correlations between total body water, extracellular fluid, and body cell mass and the drug volume of distribution or clearance and the elimination rate constant. Multiple-regression models with the all-subsets technique provided the most accurate equations with the lowest prediction errors and the highest correlation coefficients. Application of bioelectrical impedance-derived equations to a different set of patients allows prediction of pharmacokinetics. However, bioelectrical impedance equations do not yield more accurate dosing estimates than do standard dosing methods, and large dosing errors are possible in patients with aberrant physiology. Therefore, until multicenter trials in large subject populations can provide stable, accurate equations applicable to a wide variety of patient populations, bioelectrical impedance offers no advantage over standard pharmacokinetic dosing methods for the drugs studied.

Anti-Bacterial Agents↗
PubMed1996

Prophylaxis for stress-related gastrointestinal hemorrhage: a cost effectiveness analysis.

OBJECTIVE: To assess the cost-effectiveness of prophylaxis for stress-related gastrointestinal hemorrhage in patients admitted to the intensive care unit. DESIGN: Decision model of the cost and efficacy of sucralfate and cimetidine, two commonly used drugs for prophylaxis of stress-related hemorrhage. Outcome estimates were based on data from published studies. Cost data were based on cost of medications and costs of treatment protocols at our institutions. MEASUREMENTS AND MAIN RESULTS: The marginal cost-effectiveness of prophylaxis, as compare with no prophylaxis, was calculated separately for sucralfate and cimetidine and expressed as cost per bleeding episode averted. An incremental cost-effectiveness analysis was subsequently employed to compare the two agents. Sensitivity analyses of the effects of the major clinical outcomes on the cost per bleeding episode averted were performed. At the base-case assumptions of 6% risk of developing stress-related hemorrhage and 50% risk-reduction due to prophylaxis, the cost of sucralfate was $1,144 per bleeding episode averted. The cost per bleeding episode averted was highly dependent on the risk of hemorrhage and, to a lesser degree, on the efficacy of sucralfate prophylaxis, ranging from a cost per bleeding episode averted of $103,725 for low-risk patients to cost savings for very high-risk patients. The cost per bleeding episode averted increased significantly if the risk of nosocomial pneumonia was included in the analysis. The effect of pneumonia was greater for populations at low risk of hemorrhage. Assuming equal efficacy, the cost per bleeding episode averted of cimetidine was 6.5-fold greater than the cost per bleeding episode averted of sucralfate. CONCLUSIONS: The cost of prophylaxis in patients at low risk of stress-related hemorrhage is substantial, and may be prohibitive. Further research is needed to identify patient populations that are at high risk of developing stress-related hemorrhage, and to determine whether prophylaxis increases the risk of nosocomial pneumonia.

Anti-Ulcer Agents↗
PubMed1996

Is it time to reposition vasopressors and inotropes in sepsis?

OBJECTIVES: To review the literature on the current use of vasopressors and inotropes in patients with sepsis and sepsis syndrome with respect to the choice of agent, therapeutic end points, and safe and effective doses to be used. To examine the available evidence that supports or refutes goal-directed therapy toward supranormal oxygen transport in optimizing the outcome of critically ill sepsis syndrome patients. DATA SOURCES: All pertinent English and French articles dealing with hemodynamic support with selected vasopressors and inotropic agents in human sepsis and sepsis syndrome retrieved from a computerized MEDLINE search from 1985 to 1994. STUDY SELECTION: Clinical studies with norepinephrine, epinephrine, phenylephrine, dopamine, and dobutamine in sepsis syndrome were considered if goal-directed therapy with oxygen transport variables was utilized. Emphasis was placed on prospective, randomized, controlled comparative trials. However, open-label, observational, and comparative studies, or case series, were also evaluated when limited data were available. DATA EXTRACTION: From the selected studies, information was obtained regarding patient population, dosing regimen, type of therapeutic goals or end points (hemodynamic, or normal vs. supranormal oxygen transport variables) and outcome data (e.g., achievement of goals, resolution of the episode, mortality rate, and development of end-organ dysfunction). DATA SYNTHESIS: When used in larger than usual doses, epinephrine, norepinephrine, and phenylephrine uniformly increased hemodynamic values. Epinephrine may increase oxygen transport values more reliably than norepinephrine. Dobutamine doses in the range of 2.5 to 6 microgram/kg/min increase oxygen transport variables and hemodynamics to predetermined goals in only 30% to 70% of patients. Larger infusion rates offer no further benefits. CONCLUSIONS: Insufficient evidence exists to support goal-directed therapy with vasopressors and inotropes in the treatment of sepsis syndrome. No definitive recommendations can be made about the superiority of a vasopressor or inotropic agent due to the lack of data. However, it may be that evaluation of vasopressors earlier in sepsis syndrome will yield more promising results. Large, comparative, controlled trials assessing mortality rate and development of multiple organ system dysfunction are needed.

Cardiotonic Agents↗
PubMed1996

Economic impact of prolonged motor weakness complicating neuromuscular blockade in the intensive care unit.

OBJECTIVE: We compared a case-series of ten patients who developed prolonged neuromuscular weakness after continuous, nondepolarizing, neuromuscular blockade with a group of controls without neuromuscular weakness to determine the economic impact of the neuromuscular weakness. DESIGN: Frequency-matched case control trial. SETTING: Medical and surgical intensive care units of a 937-bed tertiary care, university-affiliated teaching hospital. PATIENTS: Ten patients developed prolonged neuromuscular weakness after continuous administration of nondepolarizing neuromuscular blockers. Ten patients from a 1994 drug utilization database who did not develop motor weakness after paralysis were identified to serve as controls. MEASUREMENTS AND MAIN RESULTS: The medical and accounting records of the patients were retrospectively reviewed. Charge data were obtained from patient accounts. Institutional ratios to convert charges to full costs and marginal costs were obtained from the Hospital Finance Department of Henry Ford Hospital. The economic impact of the diagnosis and recovery of the motor weakness was estimated for the intensive care unit (ICU) and hospital stays and compared with those values for control patients. Median hospital charges (excluding rehabilitation), totaling $91,476, were attributed to the patients who developed neuromuscular weakness and included charges for neuromuscular blocking agents, continuous mechanical ventilation, ICU and hospital beds, neurologic studies, and physical therapy services. In the control patients, median charges were $22,191 (p = .001). The total median cost differential for a patient in the neuromuscular weakness group was in excess of $66,713 (95% confidence interval $23,485 to $189,214, p = .001). Significant differences were also found for patient charges, full costs, and marginal costs for mechanical ventilation (p = .002), neurologic studies (p = .014), as well as ICU (p = .002) and hospital (p = .001) stays. CONCLUSIONS: The development of motor weakness was associated with an increase in ICU and hospital stays, continued mechanical ventilation, and disproportionate healthcare expenditures in excess of $66,000 per patient. A prospective evaluation of the true prevalence of neuromuscular weakness after neuromuscular blockade and of the costs to the healthcare system is needed.

Adult↗
PubMed1996

Estimation of total body and extracellular water in post-coronary artery bypass graft surgical patients using single and multiple frequency bioimpedance.

OBJECTIVE: To assess the value of bioimpedance as a clinical tool by determining the accuracy and bias of single and multiple frequency bioimpedance estimates of total body and extracellular water in comparison with values established by criterion reference techniques. DESIGN: Controlled, prospective, single-blind investigation. SETTING: Private, not-for-profit, university-affiliated, acute care hospital. PATIENTS: Eight male, post-elective coronary artery bypass graft surgical patients. INTERVENTIONS: Within 6 hrs after surgery, estimates of total body and extracellular water volumes were determined using single and multiple frequency bioimpedance techniques. These estimates were then compared with the gold standard volumes measured by deuterium oxide and bromine dilutional space determination, respectively. MEASUREMENTS AND MAIN RESULTS: The mean multiple frequency bioimpedance estimate of total body water of 47.7 +/- 9.4 L was statistically different from the single frequency bioimpedance and deuterium values of 52.5 +/- 9.4 (p < .006) and 53.3 +/- 11.6 L (p < .002), respectively. In comparison, the mean multiple and single frequency bioimpedance estimates of extracellular water, 26.3 +/- 5.4 and 29.2 +/- 5.4 L, respectively, were not statistically different from the bromine value of 27.5 +/- 6.9 L. In addition, the mean errors for multiple and single frequency bioimpedance determinations of extracellular water, -1.2 +/- 2.0 and 1.7 +/- 2.7 L, respectively, were statistically different (p = .001). CONCLUSIONS: In male, post-elective coronary artery bypass graft surgical patients, single frequency bioimpedance was a more accurate and less biased predictor of total body water than multiple frequency bioimpedance. The accuracy and bias of multiple frequency bioimpedance was superior to single frequency bioimpedance for the prediction of extracellular water. Whether this observation remains true for other populations of critically ill patients remains to be investigated.

Aged↗
PubMed1996

Technical and interpretive problems of peripheral nerve stimulation in monitoring neuromuscular blockade in the intensive care unit.

OBJECTIVE: To review the literature and provide an overview of the technical and interpretive problems associated with peripheral nerve stimulation in monitoring neuromuscular blockade in the intensive care unit. DATA SOURCES: A computerized search on MEDLINE from 1985 through 1994 was performed to identify English-language comparative studies, abstracts, and review articles pertaining to peripheral nerve stimulation, train-of-four monitoring, and neuromuscular blockade in the critical care setting. STUDY SELECTION AND DATA EXTRACTION: Relevant studies in humans were selected and information was extracted on the use of peripheral nerve monitoring in the critically ill. DATA SYNTHESIS: Use of peripheral nerve stimulation is complicated in the intensive care unit. Problems may occur with the patient, the device, as well as operator technique, all of which may lead to errors in interpretation of the depth of paralysis. The critically ill patient has changing comorbid disease states and total body water composition, which may impair the accuracy or reproducibility of measurements. Technical problems relate to the operation of the device, electrode placement, and suboptimal delivery of the desired current. Difficulties in performing peripheral nerve stimulation and interassessor variability contribute to errors of interpretation. CONCLUSIONS: These difficulties compromise the precision, accuracy, and reliability of the peripheral nerve stimulator as a tool for monitoring neuromuscular blockade in the critically ill. Peripheral nerve stimulation should be used in conjunction with clinical parameters to make decisions regarding dose adjustments. Doses should be reduced as much as possible to provide the minimum depth of paralysis that is clinically appropriate. Technical directions and training programs for peripheral nerve stimulation should be developed, and designated individuals should be trained in its application. Large, prospective, controlled studies are necessary to evaluate the incidence of prolonged paralysis or motor neuropathy with administration of neuromuscular blocking agents in patients whose dose is adjusted on the basis of peripheral nerve stimulation.

Critical Care↗
PubMed1996

Predicting unbound phenytoin concentrations in the critically ill neurosurgical patient.

OBJECTIVE: To assess the correlation of measured unbound phenytoin concentration (dphF) to estimated unbound concentration (dphEF) using the Sheiner-Tozer equation in critically ill patients in the neurosurgical intensive care unit. DESIGN: The dphF and total phenytoin (dphT) trough serum concentrations were measured during the first week of therapy in 17 consecutive patients with albumin concentrations less than 3.5 g/dL. Serum albumin concentrations were measured within 24 hours of serum phenytoin concentration measurement. SETTING: A university-affiliated urban teaching hospital. PARTICIPANTS: The study population consisted of 17 neurosurgical patients who were at least 18 years old. MAIN OUTCOME MEASURES: The predictability of the Sheiner-Tozer equation was tested by measuring dphF, dphT, and serum albumin concentrations. Measured phenytoin concentrations were compared with phenytoin concentrations calculated from the Sheiner-Tozer equation. To estimate correlation between variables linear regression was calculated. Mean absolute value of error and mean error were estimated to assess precision and bias between measures, respectively. RESULT: The mean +/- SD dphT was 13.05 +/- 5.15 mu g/mL. The measured dphF was 1.89 +/- 0.80 compared with 2.00 +/- 0.8 mu g/mL for the dphEF (NS). Regression analysis for dphEF versus dphF revealed a significant correlation (r2 = 0.94, p = 0.001). The mean absolute value of error for the Sheiner-Tozer equation to predict dphEF was 0.167, which was 9% of the mean value of dphEF (1.89). CONCLUSIONS: These results indicate that, in this population, the Sheiner-Tozer estimate of dphEF provides an unbiased, precise clinical estimate of dphF in patients for whom measured dphF is unavailable or impractical.

Adult↗
PubMed1995

Inhibition of N-acetylation of procainamide and renal clearance of N-acetylprocainamide by para-aminobenzoic acid in humans.

Procainamide administration often results in excessively high serum N-acetylprocainamide (NAPA) concentrations and subtherapeutic serum procainamide concentrations. Inhibition of N-acetylation of procainamide may prevent accumulation of excessive NAPA while maintaining therapeutic serum procainamide concentrations. The purpose of this randomized, two-way crossover study was to determine if para-aminobenzoic acid (PABA) inhibits N-acetylation of procainamide in healthy volunteers. Eleven (7 female, 4 male) fast acetylators of caffeine received, in random order, PABA 1.5 g orally every 6 hours for 5 days, with a single intravenous dose of procainamide 750 mg administered over 30 minutes on the third day, or intravenous procainamide alone. Blood samples were collected during a 48-hour period after initiation of the infusion. Urine was collected over a 72-hour period. Serum procainamide and NAPA concentrations were analyzed using fluorescence polarization immunoassay. Urine procainamide and NAPA concentrations were measured with high performance liquid chromatography. PABA did not significantly influence total or renal procainamide clearance, elimination rate constant, AUC0-00, amount of procainamide excreted unchanged in the urine, or volume of distribution. However, concomitant PABA administration with procainamide resulted in increases in NAPA AUC0-00 and t1/2 and reductions in NAPA Ke, procainamide acetylation (NAPA formation) clearance, and NAPA renal clearance. Although PABA inhibits metabolic conversion of procainamide to NAPA, it also impairs the renal clearance of NAPA (but not procainamide) in healthy subjects. Therefore, PABA may not be useful for optimizing the safety of efficacy of procainamide in patients.

4-Aminobenzoic Acid↗