Frequency of haemoglobin desaturation with the use of succinylcholine during rapid sequence induction of anaesthesia.

BACKGROUND: The perceived safety of the use of succinylcholine is based on the fact that recovery from its effects will occur before oxygen desaturation occurs in case of failure to intubate or ventilate. The purpose of this study was to examine the incidence of oxygen desaturation after the use of succinylcholine prior to resumption of spontaneous ventilation following four different preoxygenation techniques. METHODS: Twenty-five patients each were randomly allocated to preoxygenation with 4 deep breaths of 100% oxygen or by breathing oxygen for 1, 3 or 5 min following which they received a rapid sequence induction of anaesthesia with fentanyl 1 microg kg(-1), a sleep dose of thiopentone and succinylcholine 1 mg kg(-1). Oxygen saturation was monitored continuously using a finger probe. Ventilation was not assisted unless the saturation decreased to

Neostigmine antagonism of rocuronium block during anesthesia with sevoflurane, isoflurane or propofol.

PURPOSE: To examine the influence of continuing administration of sevoflurane or isoflurane during reversal of rocuronium induced neuromuscular block with neostigmine. METHODS: One hundred and twenty patients, divided into three equal groups, were randomly allocated to maintenance of anesthesia with sevoflurane, isoflurane or propofol. Neuromuscular block was induced with rocuronium and monitored using train-of-four (TOF) stimulation of the ulnar nerve and recording the force of contraction of the adductor pollicis muscle. Neostigmine was administered when the first response in TOF had recovered to 25%. At this time the volatile agent administration was stopped or propofol dosage reduced in half the patients in each group (n = 20 in each group). The times to attain TOF ratio of 0.8, and the number of patients attaining this end point within 15 min were recorded. RESULTS: The times (mean +/- SD) to recovery of the TOF ratio to 0.8 were 12.0 +/- 5.5 and 6.8 +/- 2.3 min in the sevoflurane continued and sevoflurane stopped groups, 9.0 +/- 8.3 and 5.5 +/- 3.0 min in the isoflurane continued and isoflurane stopped groups, and 5.2 +/- 2.8 and 4.7 +/- 1.5 min in the propofol continued and propofol stopped groups (P < 0.5-01). Only 9 and 15 patients in the sevoflurane and isoflurane continued groups respectively had attained a TOF ratio of 0.8 within 15 min (P < 0.001 for sevoflurane). CONCLUSIONS: The continued administration of sevoflurane, and to a smaller extent isoflurane, results in delay in attaining adequate antagonism of rocuronium induced neuromuscular block.

Postoperative residual block after intermediate-acting neuromuscular blocking drugs.

The frequency and duration of postoperative residual neuromuscular block on arrival of 150 patients in the recovery ward following the use of vecuronium (n = 50), atracurium (n = 50) and rocuronium (n = 50) were recorded. Residual block was defined as a train-of-four ratio of <0.8. An additional group of 10 patients received no neuromuscular blocking drugs during anaesthesia. The incidence of postoperative residual neuromuscular block was 64%, 52% and 39% after the use of vecuronium, atracurium and rocuronium, respectively. Similar numbers of patients were not able to maintain a sustained head or leg lift for 5 s on arrival in the recovery ward. The mean [range] times to attaining a train-of-four ratio of > or =0.8 after arrival in the recovery ward were 9.2 [1-61], 6.9 [1-24] and 14.7 [1.5-83] min for vecuronium, atracurium and rocuronium, respectively. None of the 10 patients who did not receive neuromuscular blocking drugs had train-of-four ratios <0.8 on arrival in the recovery ward. It is concluded that a large proportion of patients arrive in the recovery ward with a train-of-four ratio <0.8, even with the use of intermediate-acting neuromuscular blocking drugs. Although the residual block is relatively short lasting, it may occasionally be prolonged, requiring close observation and monitoring of such patients in the recovery ward.

Sevoflurane--nitrous oxide anaesthesia supplemented with remifentanil: effect on recovery and cognitive function.

The aim of this study was to compare recovery and psychomotor performance after maintenance of anaesthesia with sevoflurane or sevoflurane supplemented with remifentanil. Sixty-six per cent nitrous oxide was used in all patients. Twenty patients each were randomly allocated to maintenance of anaesthesia with sevoflurane only in concentrations necessary to maintain adequate anaesthesia or with 1.5, 1.0 or 0.5 MAC (end-tidal) of sevoflurane supplemented with remifentanil. The median dosage of remifentanil required in the last three groups was 0.21, 0.25 and 0.34 microg x kg(-1) x min(-1), respectively (p < 0.05). The median times to eye opening were 10.3, 12.7, 11.0 and 6.5 min in the four groups (p < 0.05 between the 0.5 MAC and the other groups) and for orientation 12.1, 14.9, 12.3 and 8.3 min, respectively (p < 0.05 between 0.5 and 1.5 MAC groups). There was no significant difference in the mini-mental state assessment scores or the actual discharge times from the recovery ward among the groups. Significantly greater numbers of patients could perform the critical flicker fusion test at 15 min in the group receiving the lowest concentration of sevoflurane and the highest dosage of remifentanil (p < 0.05). Patients in this group also showed the highest incidence of chest wall rigidity (p < 0.003). We conclude that, while the use of remifentanil with lower concentrations of sevoflurane facilitates early recovery, it does not influence discharge time from recovery ward and may be associated with side-effects such as chest wall rigidity.

Safety considerations in product development.

In drug development, about 1 in 1000 interesting compounds reaches the market. Drug safety is only relative and needs to be considered in the context of efficacy. Ultimately, the standards of safety and efficacy are determined by society. Drug safety can be enhanced by adequate patient education, i.e. patients should understand their disease as well as the risks and benefits of their medication. There is often considerable public pressure on the Government and regulatory authorities to alter some aspects of the drug development process. While we should not engage in poor science or alter regulations unthinkingly, the process should be re-examined and re-evaluated as the usual methods of evaluating risk/benefit may not be suitable for a particular disease or patient population. Public pressure has influenced changes in the USA, such as the parallel track testing, early release of drugs etc. It is important to realise that absolute toxicity is rare. Relative toxicity is more usual but may be influenced by many factors such as disease processes, drug dose, duration of administration, kinetic parameters or immunological factors. Clinical considerations in the drug development process include the predictability of adverse reactions in some patient populations, problems of over-dosage, unexpected drug-drug interactions and availability of patient monitoring. Economic factors such as total cost of the drug regimen, availability of alternative therapies, expense of sponsor-initiated special studies and surveillance, liability risk and the potential cost of altered labelling, warning notices and even market withdrawal are also considered. Thus, there are general guidelines, but the clinical, safety and toxicity considerations involved in the development of each drug may be special or unique.

The process of drug decision making: perspectives of an FDA Commissioner.

To provide drug therapy at affordable costs, critical decisions that go beyond the patient's bedside must be made. Issues regarding drug development, testing, monitoring, approval, marketing, and use must be resolved--and have been. The system through which this quality drug therapy is achieved, however, is actually no system at all. It is an integrated, economically sound, but fragile "nonsystem," in which the fundamental decisions are made by us. Unless our criteria, our needs, and our expectations are entered into the drug decision-making process, we cannot expect to be satisfied with the outcome.

The Food and Drug Administration's role in the canned salmon recalls of 1982.

The Alaska salmon industry conducted 9 recalls of 7 3/4-oz cans of salmon in 1982 after a 7 3/4-oz can of Alaskan salmon was implicated in illness and one death in Belgium from Clostridium botulinum type E toxin. By the code number on the can, the Food and Drug Administration (FDA), Seattle District, traced it to a specific salmon packer. Subsequently, the FDA received a report about a defect in the can. Investigation of the salmon packer's plant by the Agency revealed that the equipment used at the plant to reform the cans--which arrived at the cannery in a nearly flattened state--might have been responsible for the defect. The death and illness in Belgium, combined with the results of the FDA inspection of the plant implicated in the Belgian incident, provided strong evidence of the existence of a hazardous situation that might have widespread adverse health effects. The Food and Drug Administration therefore requested the firm to recall its 1980 and 1981 production of salmon packaged in 7 3/4-oz cans. The Agency then began an investigation of all U.S. salmon packed inn cans of this size that had been reformed on the equipment implicated in the can defect. Of 300,000 cans examined, 22 with the defect were found. As additional firms were identified as having used the defective cans, subsequent recalls were initiated.

United States Food and Drug Administration approach to risk evaluation and risk management for foods.

The Food and Drug Administration (FDA) is developing a comprehensive program on risk evaluation and risk management related to foods and food ingredients. Various groups view the FDA differently in terms of potential food hazards, but the regulatory agency is required to follow the laws that reflect a set of social judgments about permissible risks and benefits. The traditional agency approaches to risk management are reviewed and recent plans to consider structural changes in the basic food statute that could lead to greater administrative flexibility are presented. The proposed tentative suggestions discussed embody basic principles that the public health and trust remain the focus of food safety laws. Public confidence in the present system must be retained, it must be a credible system, embody valid scientific data, and the regulatory actions must be taken by FDA scientists who are recognized for their scientific competence. All the proposed actions need to be taken without placing unnecessary economic burdens on industry. The scope of this program is reviewed.

FDA's dietary sodium initiative--in the war against hypertension, a new weapon.

The Food and Drug Administration is engaged in a broad-based program to make consumers more aware of the potential impact on health of sodium consumption well in excess of dietary needs; to encourage food manufacturers to lower the amounts of sodium they add to their products, where this is safe and feasible; and to provide information to consumers about the sodium content of the foods they buy and use. This program is expected to be a significant preventive public health measure against hypertension.

Captopril-induced skin eruptions.

Seven of 23 hypertensive patients treated with captopril (SQ 14,225), an orally active converting enzyme inhibitor, developed a pruritic, erythematous, macular, and papular eruption of the trunk, face, and proximal extremities. The eruption appeared one to 31 weeks after initiation of captopril therapy and was associated with diarrhea (three patients), fever (two patients), and generalized arthralgias (one patient). Six patients had an increased percentage of band cells (5 to 34 per cent) on peripheral smear without an associated leukocytosis. In one patient, the skin rash was associated with a peripheral eosinophilia (20 per cent). Coombs-positive hemolytic anemia, and acute renal failure with eosinophiluria. There were no changes in BUN, creatinine, or urinalyses in the remaining patients. Four patients showed a transient rise in plasma PGE without concomitant changes in plasma PFG2 alpha or 6-keto PGF1 alpha, and three patients had slight elevations in the erythrocyte sedimentation rate. Skin biopsies revealed a perivascular and perifollicular lymphocytic and histiocytic infiltrate with negative immunofluorescence to IgG, IgM, IgA, and beta 1 C. The skin eruption and associated symptoms resolved in all patients, even though captopril administration was continued in six of the seven patients.

Current FDA directives for promoting public health.

The current directions of the FDA are outlined. The underlying philosophy of the FDA under the Reagan Administration is that both the private sector and the government must address the responsibilities to which they are best suited for the health-care system to work more efficiently. To facilitate this, FDA is conducting comprehensive reviews of FDA regulations and the drug-evaluation process. There are many dimensions to promoting public health, and the FDA alone cannot assure an adequate supply of safe and effective drugs. Innovative science and technology are needed to develop new drugs, followed by maximum potentiation (maximum good and least harm) after FDA approval. Hospital pharmacists have a role in maximizing the potential benefits of drugs through pharmacy and therapeutics committees. The current status of the pilot program for patient package inserts is described. The response at a recent hearing on the program indicates that the responsibility to protect the public health is shared by the government, health professions, industry, and the public. The FDA's campaign on sodium is based on that shared responsibility. By improving communication and building upon their common objections, both pharmacy and the FDA can do their jobs successfully.

Converting enzyme inhibition with captopril in patients with primary hyperaldosteronism.

The humoral and hemodynamic effects of converting enzyme inhibition captopril are presented in two patients with primary hyperaldosteronism (PHA). In all, 20 patients with resistant hypertension were treated with the angiotensin converting enzyme inhibitor captopril. In 18 patients with essential or renovascular hypertension mean (+/- SEM) plasma renin activity (PRA) rose from 5.0 +/- 1.4 to 35.3 +/- 5.3 ng/ml/hr (P less than 0.01) and mean (+/- SEM) plasma aldosterone (PA) declined from 25.8 +/- 2.9 to 15.1 +/- 1.9 ng/ml (P less than 0.01) after captopril. In two patients with PHA the PRA was not stimulated by converting enzyme inhibition, although there was modest decline in PA and a temporary reduction in blood pressure. After surgical removal of aldosterone-producing adenomas, PRA responsed appropriately to captopril. These cases illustrate that a disease process can modify the response to a drug and demonstrate that, in patients with PHA, captopril does not stimulate PRA, induces only minor decrements in PA, and is relatively ineffective as an antihypertensive.