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The Cochrane Database of Systematic... Oct 2020Postoperative nausea and vomiting (PONV) is a common adverse effect of anaesthesia and surgery. Up to 80% of patients may be affected. These outcomes are a major cause... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Postoperative nausea and vomiting (PONV) is a common adverse effect of anaesthesia and surgery. Up to 80% of patients may be affected. These outcomes are a major cause of patient dissatisfaction and may lead to prolonged hospital stay and higher costs of care along with more severe complications. Many antiemetic drugs are available for prophylaxis. They have various mechanisms of action and side effects, but there is still uncertainty about which drugs are most effective with the fewest side effects.
OBJECTIVES
• To compare the efficacy and safety of different prophylactic pharmacologic interventions (antiemetic drugs) against no treatment, against placebo, or against each other (as monotherapy or combination prophylaxis) for prevention of postoperative nausea and vomiting in adults undergoing any type of surgery under general anaesthesia • To generate a clinically useful ranking of antiemetic drugs (monotherapy and combination prophylaxis) based on efficacy and safety • To identify the best dose or dose range of antiemetic drugs in terms of efficacy and safety SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), ClinicalTrials.gov, and reference lists of relevant systematic reviews. The first search was performed in November 2017 and was updated in April 2020. In the update of the search, 39 eligible studies were found that were not included in the analysis (listed as awaiting classification).
SELECTION CRITERIA
Randomized controlled trials (RCTs) comparing effectiveness or side effects of single antiemetic drugs in any dose or combination against each other or against an inactive control in adults undergoing any type of surgery under general anaesthesia. All antiemetic drugs belonged to one of the following substance classes: 5-HT₃ receptor antagonists, D₂ receptor antagonists, NK₁ receptor antagonists, corticosteroids, antihistamines, and anticholinergics. No language restrictions were applied. Abstract publications were excluded.
DATA COLLECTION AND ANALYSIS
A review team of 11 authors independently assessed trials for inclusion and risk of bias and subsequently extracted data. We performed pair-wise meta-analyses for drugs of direct interest (amisulpride, aprepitant, casopitant, dexamethasone, dimenhydrinate, dolasetron, droperidol, fosaprepitant, granisetron, haloperidol, meclizine, methylprednisolone, metoclopramide, ondansetron, palonosetron, perphenazine, promethazine, ramosetron, rolapitant, scopolamine, and tropisetron) compared to placebo (inactive control). We performed network meta-analyses (NMAs) to estimate the relative effects and ranking (with placebo as reference) of all available single drugs and combinations. Primary outcomes were vomiting within 24 hours postoperatively, serious adverse events (SAEs), and any adverse event (AE). Secondary outcomes were drug class-specific side effects (e.g. headache), mortality, early and late vomiting, nausea, and complete response. We performed subgroup network meta-analysis with dose of drugs as a moderator variable using dose ranges based on previous consensus recommendations. We assessed certainty of evidence of NMA treatment effects for all primary outcomes and drug class-specific side effects according to GRADE (CINeMA, Confidence in Network Meta-Analysis). We restricted GRADE assessment to single drugs of direct interest compared to placebo.
MAIN RESULTS
We included 585 studies (97,516 randomized participants). Most of these studies were small (median sample size of 100); they were published between 1965 and 2017 and were primarily conducted in Asia (51%), Europe (25%), and North America (16%). Mean age of the overall population was 42 years. Most participants were women (83%), had American Society of Anesthesiologists (ASA) physical status I and II (70%), received perioperative opioids (88%), and underwent gynaecologic (32%) or gastrointestinal surgery (19%) under general anaesthesia using volatile anaesthetics (88%). In this review, 44 single drugs and 51 drug combinations were compared. Most studies investigated only single drugs (72%) and included an inactive control arm (66%). The three most investigated single drugs in this review were ondansetron (246 studies), dexamethasone (120 studies), and droperidol (97 studies). Almost all studies (89%) reported at least one efficacy outcome relevant for this review. However, only 56% reported at least one relevant safety outcome. Altogether, 157 studies (27%) were assessed as having overall low risk of bias, 101 studies (17%) overall high risk of bias, and 327 studies (56%) overall unclear risk of bias. Vomiting within 24 hours postoperatively Relative effects from NMA for vomiting within 24 hours (282 RCTs, 50,812 participants, 28 single drugs, and 36 drug combinations) suggest that 29 out of 36 drug combinations and 10 out of 28 single drugs showed a clinically important benefit (defined as the upper end of the 95% confidence interval (CI) below a risk ratio (RR) of 0.8) compared to placebo. Combinations of drugs were generally more effective than single drugs in preventing vomiting. However, single NK₁ receptor antagonists showed treatment effects similar to most of the drug combinations. High-certainty evidence suggests that the following single drugs reduce vomiting (ordered by decreasing efficacy): aprepitant (RR 0.26, 95% CI 0.18 to 0.38, high certainty, rank 3/28 of single drugs); ramosetron (RR 0.44, 95% CI 0.32 to 0.59, high certainty, rank 5/28); granisetron (RR 0.45, 95% CI 0.38 to 0.54, high certainty, rank 6/28); dexamethasone (RR 0.51, 95% CI 0.44 to 0.57, high certainty, rank 8/28); and ondansetron (RR 0.55, 95% CI 0.51 to 0.60, high certainty, rank 13/28). Moderate-certainty evidence suggests that the following single drugs probably reduce vomiting: fosaprepitant (RR 0.06, 95% CI 0.02 to 0.21, moderate certainty, rank 1/28) and droperidol (RR 0.61, 95% CI 0.54 to 0.69, moderate certainty, rank 20/28). Recommended and high doses of granisetron, dexamethasone, ondansetron, and droperidol showed clinically important benefit, but low doses showed no clinically important benefit. Aprepitant was used mainly at high doses, ramosetron at recommended doses, and fosaprepitant at doses of 150 mg (with no dose recommendation available). Frequency of SAEs Twenty-eight RCTs were included in the NMA for SAEs (10,766 participants, 13 single drugs, and eight drug combinations). The certainty of evidence for SAEs when using one of the best and most reliable anti-vomiting drugs (aprepitant, ramosetron, granisetron, dexamethasone, ondansetron, and droperidol compared to placebo) ranged from very low to low. Droperidol (RR 0.88, 95% CI 0.08 to 9.71, low certainty, rank 6/13) may reduce SAEs. We are uncertain about the effects of aprepitant (RR 1.39, 95% CI 0.26 to 7.36, very low certainty, rank 11/13), ramosetron (RR 0.89, 95% CI 0.05 to 15.74, very low certainty, rank 7/13), granisetron (RR 1.21, 95% CI 0.11 to 13.15, very low certainty, rank 10/13), dexamethasone (RR 1.16, 95% CI 0.28 to 4.85, very low certainty, rank 9/13), and ondansetron (RR 1.62, 95% CI 0.32 to 8.10, very low certainty, rank 12/13). No studies reporting SAEs were available for fosaprepitant. Frequency of any AE Sixty-one RCTs were included in the NMA for any AE (19,423 participants, 15 single drugs, and 11 drug combinations). The certainty of evidence for any AE when using one of the best and most reliable anti-vomiting drugs (aprepitant, ramosetron, granisetron, dexamethasone, ondansetron, and droperidol compared to placebo) ranged from very low to moderate. Granisetron (RR 0.92, 95% CI 0.80 to 1.05, moderate certainty, rank 7/15) probably has no or little effect on any AE. Dexamethasone (RR 0.77, 95% CI 0.55 to 1.08, low certainty, rank 2/15) and droperidol (RR 0.89, 95% CI 0.81 to 0.98, low certainty, rank 6/15) may reduce any AE. Ondansetron (RR 0.95, 95% CI 0.88 to 1.01, low certainty, rank 9/15) may have little or no effect on any AE. We are uncertain about the effects of aprepitant (RR 0.87, 95% CI 0.78 to 0.97, very low certainty, rank 3/15) and ramosetron (RR 1.00, 95% CI 0.65 to 1.54, very low certainty, rank 11/15) on any AE. No studies reporting any AE were available for fosaprepitant. Class-specific side effects For class-specific side effects (headache, constipation, wound infection, extrapyramidal symptoms, sedation, arrhythmia, and QT prolongation) of relevant substances, the certainty of evidence for the best and most reliable anti-vomiting drugs mostly ranged from very low to low. Exceptions were that ondansetron probably increases headache (RR 1.16, 95% CI 1.06 to 1.28, moderate certainty, rank 18/23) and probably reduces sedation (RR 0.87, 95% CI 0.79 to 0.96, moderate certainty, rank 5/24) compared to placebo. The latter effect is limited to recommended and high doses of ondansetron. Droperidol probably reduces headache (RR 0.76, 95% CI 0.67 to 0.86, moderate certainty, rank 5/23) compared to placebo. We have high-certainty evidence that dexamethasone (RR 1.00, 95% CI 0.91 to 1.09, high certainty, rank 16/24) has no effect on sedation compared to placebo. No studies assessed substance class-specific side effects for fosaprepitant. Direction and magnitude of network effect estimates together with level of evidence certainty are graphically summarized for all pre-defined GRADE-relevant outcomes and all drugs of direct interest compared to placebo in http://doi.org/10.5281/zenodo.4066353.
AUTHORS' CONCLUSIONS
We found high-certainty evidence that five single drugs (aprepitant, ramosetron, granisetron, dexamethasone, and ondansetron) reduce vomiting, and moderate-certainty evidence that two other single drugs (fosaprepitant and droperidol) probably reduce vomiting, compared to placebo. Four of the six substance classes (5-HT₃ receptor antagonists, D₂ receptor antagonists, NK₁ receptor antagonists, and corticosteroids) were thus represented by at least one drug with important benefit for prevention of vomiting. Combinations of drugs were generally more effective than the corresponding single drugs in preventing vomiting. NK₁ receptor antagonists were the most effective drug class and had comparable efficacy to most of the drug combinations. 5-HT₃ receptor antagonists were the best studied substance class. For most of the single drugs of direct interest, we found only very low to low certainty evidence for safety outcomes such as occurrence of SAEs, any AE, and substance class-specific side effects. Recommended and high doses of granisetron, dexamethasone, ondansetron, and droperidol were more effective than low doses for prevention of vomiting. Dose dependency of side effects was rarely found due to the limited number of studies, except for the less sedating effect of recommended and high doses of ondansetron. The results of the review are transferable mainly to patients at higher risk of nausea and vomiting (i.e. healthy women undergoing inhalational anaesthesia and receiving perioperative opioids). Overall study quality was limited, but certainty assessments of effect estimates consider this limitation. No further efficacy studies are needed as there is evidence of moderate to high certainty for seven single drugs with relevant benefit for prevention of vomiting. However, additional studies are needed to investigate potential side effects of these drugs and to examine higher-risk patient populations (e.g. individuals with diabetes and heart disease).
Topics: Adult; Anesthesia, General; Antiemetics; Drug Therapy, Combination; Female; Humans; Male; Network Meta-Analysis; Placebos; Postoperative Nausea and Vomiting; Randomized Controlled Trials as Topic
PubMed: 33075160
DOI: 10.1002/14651858.CD012859.pub2 -
Medical Principles and Practice :... 2022Several forms of cannabinoids are currently being used to manage nausea and vomiting (N/V). Emerging cases of refractory N/V associated with chronic cannabis use among...
INTRODUCTION
Several forms of cannabinoids are currently being used to manage nausea and vomiting (N/V). Emerging cases of refractory N/V associated with chronic cannabis use among adults and older patients have been reported named cannabis hyperemesis syndrome (CHS). CHS is a condition that leads to repeated and severe N/V in long-term users of cannabinoids.
OBJECTIVE
The aim of this study was to outline current treatments for the management of CHS.
METHODS
A systematic review was conducted using PubMed, Ovid MEDLINE, Cochrane Central, EMBASE, and Google Scholar. Databases were used to search for articles on CHS published from January 2009 to June 2021, yielding 225 results of which 17 were deemed relevant and underwent review by 2 separate reviewers.
RESULTS
The duration of cannabis administration ranged between 6 months to 11 years may precipitate symptoms of CHS. The Rome IV diagnostic criteria of CHS require cannabinoid use and persistence of N/V symptoms for at least the past 6 months. Cannabis cessation is noted to be the most successful management, but other treatments also demonstrated symptom relief; these include hot water hydrotherapy, topical capsaicin cream, haloperidol, droperidol, benzodiazepines, propranolol, and aprepitant administration.
CONCLUSION
More research on CHS is needed to enhance knowledge translation, education, and create awareness in the medical community on the side effects of cannabinoids and to propose the best treatment options.
Topics: Adult; Analgesics; Cannabinoids; Cannabis; Humans; Marijuana Abuse; Syndrome; Vomiting
PubMed: 34724666
DOI: 10.1159/000520417 -
The American Journal of Emergency... Jan 2022Safe and effective tranquilization of the acutely agitated patient is challenging, and head-to-head comparisons of medications are limited. We aimed to identify the most... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Safe and effective tranquilization of the acutely agitated patient is challenging, and head-to-head comparisons of medications are limited. We aimed to identify the most optimal agent(s) for rapid tranquilization of the severely agitated patient in the emergency department (ED).
METHODS
The protocol for systematic review was registered (PROSPERO; CRD42020212534). We searched MEDLINE, Embase, PsycINFO, and Cochrane Database/CENTRAL from inception to June 2, 2021. We limited studies to randomized controlled trials that enrolled adult ED patients with severe agitation and compared drugs for rapid tranquilization. Predetermined outcomes were: 1) Adequate sedation within 30 min (effectiveness), 2) Immediate, serious adverse event - cardiac arrest, ventricular tachydysrhythmia, endotracheal intubation, laryngospasm, hypoxemia, hypotension (safety), and 3) Time to adequate sedation (effect onset). We extracted data according to PRISMA-NMA and appraised trials using Cochrane RoB 2 tool. We performed Bayesian network meta-analysis (NMA) using a Markov Chain Monte Carlo method with random-effects model and vague prior distribution to calculate odds ratios with 95% credible intervals for dichotomous outcomes and frequentist NMA to calculate mean differences with 95% confidence intervals for continuous outcomes. We assessed confidence in results using CINeMA. We used surface under the cumulative ranking (SUCRA) curves to rank agent(s) for each outcome.
RESULTS
Eleven studies provided data for effectiveness (1142 patients) and safety (1147 patients). Data was insufficient for effect onset. The NMA found that ketamine (SUCRA = 93.0%) is most likely to have superior effectiveness; droperidol-midazolam (SUCRA = 78.8%) is most likely to be safest. There are concerns with study quality and imprecision. Quality of the point estimates varied for effectiveness but mostly rated "very low" for safety.
CONCLUSIONS
Available evidence suggests that ketamine and droperidol have intermediate effectiveness for rapid tranquilization of the severely agitated patient in the ED. There is insufficient evidence to definitively determine which agent(s) may be safest or fastest-acting. Further, direct-comparison study of ketamine and droperidol is recommended.
Topics: Adult; Droperidol; Emergence Delirium; Emergency Service, Hospital; Humans; Ketamine; Network Meta-Analysis; Psychomotor Agitation; Randomized Controlled Trials as Topic; Severity of Illness Index; Treatment Outcome
PubMed: 34823192
DOI: 10.1016/j.ajem.2021.11.011 -
The New England Journal of Medicine Jun 2004Untreated, one third of patients who undergo surgery will have postoperative nausea and vomiting. Although many trials have been conducted, the relative benefits of... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
BACKGROUND
Untreated, one third of patients who undergo surgery will have postoperative nausea and vomiting. Although many trials have been conducted, the relative benefits of prophylactic antiemetic interventions given alone or in combination remain unknown.
METHODS
We enrolled 5199 patients at high risk for postoperative nausea and vomiting in a randomized, controlled trial of factorial design that was powered to evaluate interactions among as many as three antiemetic interventions. Of these patients, 4123 were randomly assigned to 1 of 64 possible combinations of six prophylactic interventions: 4 mg of ondansetron or no ondansetron; 4 mg of dexamethasone or no dexamethasone; 1.25 mg of droperidol or no droperidol; propofol or a volatile anesthetic; nitrogen or nitrous oxide; and remifentanil or fentanyl. The remaining patients were randomly assigned with respect to the first four interventions. The primary outcome was nausea and vomiting within 24 hours after surgery, which was evaluated blindly.
RESULTS
Ondansetron, dexamethasone, and droperidol each reduced the risk of postoperative nausea and vomiting by about 26 percent. Propofol reduced the risk by 19 percent, and nitrogen by 12 percent; the risk reduction with both of these agents (i.e., total intravenous anesthesia) was thus similar to that observed with each of the antiemetics. All the interventions acted independently of one another and independently of the patients' baseline risk. Consequently, the relative risks associated with the combined interventions could be estimated by multiplying the relative risks associated with each intervention. Absolute risk reduction, though, was a critical function of patients' baseline risk.
CONCLUSIONS
Because antiemetic interventions are similarly effective and act independently, the safest or least expensive should be used first. Prophylaxis is rarely warranted in low-risk patients, moderate-risk patients may benefit from a single intervention, and multiple interventions should be reserved for high-risk patients.
Topics: Anesthesia, General; Anesthesia, Intravenous; Anesthesia, Local; Anesthetics, Intravenous; Antiemetics; Dexamethasone; Droperidol; Drug Therapy, Combination; Factor Analysis, Statistical; Female; Fentanyl; Humans; Logistic Models; Male; Multivariate Analysis; Nitrogen; Nitrous Oxide; Ondansetron; Piperidines; Postoperative Nausea and Vomiting; Premedication; Propofol; Remifentanil; Single-Blind Method
PubMed: 15190136
DOI: 10.1056/NEJMoa032196 -
Journal of Education & Teaching in... Oct 2020This scenario was developed to educate emergency medicine residents about the diagnosis and management of the agitated psychiatric patient.
AUDIENCE
This scenario was developed to educate emergency medicine residents about the diagnosis and management of the agitated psychiatric patient.
INTRODUCTION
The prevalence of agitation among patients in the emergency department is increasing, with an estimated 1.7 million events occurring annually in the United States.1 There are various methodologies for de-escalation, including verbal and chemical de-escalation and physical restraints. Chemical and/or physical restraints are sometimes necessary to ensure patient and staff safety when verbal de-escalation is ineffective, particularly since agitation is the leading cause of hospital staff injuries.2 Chemical restraints have been shown to be less physically traumatizing to patients.3 4 Adverse events associated with physical restraints include persistent psychological distress, blunt chest trauma, aspiration, respiratory depression, and asphyxiation leading to cardiac arrest.5 In regards to chemical restraints, adverse event reporting has been heterogeneous among studies, but the most consistent reported events involve respiratory compromise such as desaturation, airway obstruction, and respiratory depression.3 A study measuring QTc (corrected QT interval) after high-dose intramuscular ziprasidone or haloperidol did not demonstrate any QTc longer than 480 msec.6 Other events linked to chemical restraints include uncommon cardiovascular events and extrapyramidal side effects from medications.3 The main classes of medications utilized for chemical restraint include first-generation antipsychotics (eg, haloperidol and droperidol), second-generation antipsychotics (olanzapine, quetiapine, risperidone, aripiprazole, and ziprasidone), benzodiazipenes (eg, lorazepam and midazolam), and N-methyl-D-aspartic acid (NMDA) receptor antagonists (eg, ketamine).7,8 It is important to exclude other medical causes of agitation, consider the differential diagnoses, and then select a medication that is tailored to address underlying etiologies while remaining cognizant of the side effect profiles of these chemical agents.: At the conclusion of the simulation session, learners will be able to: 1) Obtain a relevant focused history and physical examination on the agitated psychiatric patient. 2) Develop a differential for the agitated psychiatric patient, including primary psychiatric conditions and other organic pathologies. 3) Discuss the management of the agitated psychiatric patient, including the different options available for chemical sedation. 4) Prioritize safety of self and staff when caring for an agitated psychiatric patient.
EDUCATIONAL METHODS
This session was conducted using simulation with a standardized patient, followed by a debriefing session and lecture on the presentation, differential diagnosis, and management of the agitated psychiatric patient. Debriefing methods may be left to the discretion of participants, but the authors have utilized advocacy-inquiry techniques. This scenario may also be run as an oral board examination case.
RESEARCH METHODS
The residents are provided a survey at the completion of the debriefing session to rate different aspects of the simulation, as well as provide qualitative feedback on the scenario. This survey is specific to the local institution's simulation center.
RESULTS
Feedback from the residents was overwhelmingly positive, although many stated that they felt some degree of intimidation or stress from the standardized patient who did not break from their role throughout the scenario.The local institution's simulation center feedback form is based on the Center of Medical Simulation's Debriefing Assessment for Simulation in Healthcare (DASH) Student Version Short Form9 with the inclusion of required qualitative feedback if an element was scored less than a 6 or 7. This session received mostly 7 scores (extremely effective/outstanding).
DISCUSSION
This is a physically safe method for reviewing management of the agitated psychiatric patient. There are multiple potential presentations of the agitated psychiatric patient, as well as varying underlying etiologies. These scenarios may be tailored to the needs of the learner, including identifying agitation, pharmacologic review, and de-escalation techniques.
TOPICS
Medical simulation, agitated psychiatric patient, chemical sedation, verbal de-escalation, emergency medicine, psychiatry.
PubMed: 37465334
DOI: 10.21980/J85352 -
Ci Ji Yi Xue Za Zhi = Tzu-chi Medical... 2018Droperidol is a short-acting, potent dopamine D2 antagonist that can pass through the blood-brain barrier. A black box warning was issued for droperidol by the United... (Review)
Review
Droperidol is a short-acting, potent dopamine D2 antagonist that can pass through the blood-brain barrier. A black box warning was issued for droperidol by the United States Food and Drug Administration in 2001 because of a risk of development of torsades de pointes induced by QT prolongation. Many experts feel that the incidence of arrhythmia is overestimated, and low-dose droperidol is almost always used by anesthesiologists for postoperative nausea and vomiting. In this review, we used evidence-based analysis to appraise high-quality studies with a low risk of bias published after 2001 on the use of droperidol in the emergency department (ED). Droperidol appears not only efficacious but also safe to treat patients with nausea/vomiting, acute psychosis, and migraine in the ED. For these conditions, droperidol may be an option for shared decision-making.
PubMed: 29643708
DOI: 10.4103/tcmj.tcmj_195_17 -
Anaesthesia Nov 2009
Topics: Anesthesiology; Antiemetics; Droperidol; Drug Administration Schedule; Drug Therapy, Combination; Humans; Long QT Syndrome; Postoperative Nausea and Vomiting
PubMed: 19825047
DOI: 10.1111/j.1365-2044.2009.06124.x -
Anesthesiology Nov 1980In MH, skeletal muscle acutely and unexpectedly increases its oxygen consumption and lactate production, resulting in greater heat production, respiratory and metabolic... (Review)
Review
In MH, skeletal muscle acutely and unexpectedly increases its oxygen consumption and lactate production, resulting in greater heat production, respiratory and metabolic acidosis, muscle ridigity, sympathetic stimulation, and increased cellular permeability. The best-accepted theory is that MH is due to an inability to control calcium concentrations within the muscle fiber, and may involve a generalized alteration in cellular or subcellular membrane permeability. Episodes are predictably initiated in susceptible people and swine by potent volative anethetic agents or succinylcholine. In addition, in swine, MH is consistently triggered by excitement, apprehension, exercise, or environmental stress such as heat or hypoxia. Several genetic factors probably control the human and porcine inheritance of MH. Sympathetic involvement in MH, while controversial, is probably a response to stress that affects blood flow, heat loss, and myocardial function, rather than a direct sympathetic activation of susceptible muscle. Diagnosis is based upon extraordinary temperature and acid-base and muscle aberrations. Specific treatment is the action of dantrolene upon muscle calcium movements; sympatomatic treatment is by reversal of acid-base and temperature changes. Evaluation of affected families is guided by measurements of circulating creatine phosphokinase and by analysis of drug-induced contractures in muscle biopsy specimens. Anesthesia for susceptible patients includes thiopental, opiates, droperidol, pancuronium, nitrous oxide, and preoperative oral doses of dantrolene.
Topics: Adult; Anesthesia; Animals; Creatine Kinase; Disease Models, Animal; Humans; Legislation, Medical; Male; Malignant Hyperthermia; Muscles; Myocardium; Rabbits; Rats; Swine; Syndrome; United States
PubMed: 6999950
DOI: 10.1097/00000542-198011000-00007