Bertil K.J. Wagner

Pharmacokinetics and Pharmacodynamics of Sedatives and Analgesics in the Treatment of Agitated Critically Ill Patients

SummaryThe pharmacokinetics and pharmacodynamics of sedatives and analgesics are significantly altered in the critically ill. These changes may account for the large differences in drug dosage requirements compared with other patient populations. Drugs that in other settings may be considered short-acting often have significantly altered onset and duration of action in critically ill patients, necessitating a change in dosage.Of the benzodiazepines, lorazepam is the drug whose parameters are the least likely to be altered in critical illness. The presence of active metabolites with other benzodiazepines complicates their use during periods of prolonged use. Similarly, the presence of active metabolites of morphine and pethidine (meperidine) warrants caution in patients with renal insufficiency. The fewer cardiovascular effects seen with high-potency opioids, such as fentanyl and sufentanil, increase their usefulness in haemodynamically compromised patients. The pharmacodynamics of propofol are not significantly altered in the critically ill. Ketamine should be used with a benzodiazepine to prevent the emergence of psychomimetic reactions. Lower sedative doses of benzodiazepines and anaesthetics may not provide reliable amnesia.Barbiturates and propofol probably do not induce hyperalgesia and lack intrinsic analgesic activity. The antipsychotic agent haloperidol has a calming effect on patients and administration to the point of sedation is generally not necessary. Combinations of sedatives and analgesics are synergistic in producing sedation.The costs of sedation and analgesia are very variable and closely linked to the pharmacokinetics and pharmacodynamics of the drug. Monitoring of sedation and analgesia is difficult in uncooperative patients in the intensive care unit. In the future, specific monitoring tools may assist clinicians in the regulation of infusions of sedative and analgesic agents.

Efficacy and Safety of Patient-Controlled Analgesia for Morbidly Obese Patients Following Gastric Bypass Surgery

Background: Adequate postoperative pain control is important to reduce potential cardiopulmonary complications. It is often difficult to determine dosages of narcotics for morbidly obese patients following Rouxen-Y gastric bypass (RYGBP) due to respiratory depression. Individualization of analgesic therapy, patient-controlled analgesia (PCA), can provide optimal dosage for pain control and minimize the side-effects. Method: 25 morbidly obese patients who received PCA with morphine sulfate following RYGBP. PCA settings we re as follows: morphine, 20 µg/kg of ideal body weight, 10-minute lock out interval and 80% of a calculated amount for a 4-hour limit.We measured arterial blood gas, heart rate, mean arterial pressure, arterial oxygen saturation, respiratory rate, opioid amount, patient satisfaction, visual analog pain scale (VAS), and the incidence of nausea, vomiting, pruritus and sedation. Results: Average morphine usage was 44.2±28.7 mg during the day of surgery (DOS); 49.1±27.4 mg during POD (postoperative day) #1; and 36.6±22.8 mg during POD#2 (p < 0.01). 24 patients were satisfied with their pain control on POD#1. VAS was 5.4±2.1 on the day of surgery, but remained below 4 thereafter. Arterial oxygen saturation and vital signs were maintained without significant changes. 5 patients experienced mild sedation on the day of surgery and 3 patients experienced mild sedation on POD#1. 1 patient experienced nausea and vomiting and 4 patients had pruritus; however, none required treatment. Conclusion: PCA is safe and effective for morbidly obese patients following RYGBP.

Comparison of intranasal midazolam and sufentanil premedication in pediatric outpatients.

Intranasally administered midazolam was compared with sufentanil as a premedicant for 60 patients, aged ½ to 6 years, undergoing outpatient surgery of 2 hours or less.

Patient recall of therapeutic paralysis in a surgical critical care unit.

Study Objective. To investigate patient recall of therapeutic paralysis (TP) in a surgical critical care unit.

Retrospective analysis of postoperative nausea and vomiting to determine antiemetic activity of droperidol added to propofol : a possible drug interaction

Propofol decreases the frequency of postoperative nausea and vomiting. We investigated whether its antiemetic activity could be improved further by coadministration of droperidol. We retrospectively reviewed the records of 266 women who underwent laparoscopic operations with nitrous oxide anesthesia and thiopental or propofol induction. The records were screened for frequency and time of occurrence of nausea and vomiting, concurrent drug use, duration of surgery, and times of recovery room admission and discharge. The combination of droperidol and thiopental decreased the frequency of nausea and vomiting over droperidol plus propofol, propofol alone, and thiopental alone. The addition of droperidol to propofol anesthesia doubled the frequency of multiple nausea and vomiting episodes, suggesting a possible interaction between the drugs. We cannot recommend that droperidol be added to propofol anesthesia for prophylaxis of postoperative nausea and vomiting.

Cefotetan Disodium-Induced Hemolytic Anemia

OBJECTIVE: To report a case of cefotetan disodium-induced hemolytic anemia. DATA SOURCES: Original research articles and case reports. DATA SYNTHESIS: A 46-year-old woman developed fulminant hemolytic anemia following a second exposure to intravenous cefotetan disodium for postoperative prophylaxis. She developed respiratory failure requiring intubation and acute renal failure requiring hemodialysis. The hemolysis was successfully treated with plasmapheresis, but the patient died on the 25th postoperative day. Positive Coombs tests have been reported in less than three percent of patients receiving cefotetan. To our knowledge, this is the first case of fulminant hemolytic anemia associated with intravenous cefotetan disodium therapy. CONCLUSIONS: Cefotetan should be added to the list of drugs known to cause hemolytic anemia. Monitoring for hemolysis should be considered for patients who receive multiple courses of therapy.

Cost analysis of propofol versus thiopental induction anesthesia in outpatient laparoscopic gynecologic surgery.

This study investigated the cost of propofol versus thiopental anesthesia in 243 patients who underwent outpatient laparoscopic gynecologic surgery. Patients records were analyzed for medication use, duration of surgery, anesthesia, recovery room stay, and associated costs. Despite the higher drug cost for propofol, the total mean cost was

A Double-Blind, Placebo-Controlled Evaluation of Intranasal Metoclopramide in the Prevention of Postoperative Nausea and Vomiting

273.00 less per patient for patients receiving propofol induction anesthesia. Extension of these data translates into cost savings of approximately

Effects of Intravenous Famotidine on Gastric Acid Secretion in Patients Undergoing Cardiac Surgery

7900.00 if propofol had been used for all patients. Although the duration of surgery for the propofol group was shorter by nearly 12 minutes, the anesthesia duration and recovery room stay were both longer for the thiopental group, reflecting the longer duration of action of thiopental. Although the realized cost savings of drugs, surgery, anesthesia, and recovery time when propofol versus thiopental is used for outpatient laparoscopic gynecologic surgery are relatively small on an individual patient basis, cost savings may become more significant if larger patient populations are studied.

Pharmacoeconomic Analysis of Sevoflurane versus Isoflurane Anesthesia in Elective Ambulatory Surgery

Nausea and vomiting are common complaints in the postoperative period and contribute to patient distress and delay of discharge for outpatient surgical procedures. Laparoscopic procedures are associated with a high incidence of postoperative nausea and vomiting (PONV) episodes. Parenteral use of metoclopramide prevents and treats PONV. The intranasal route provides rapid and complete absorption of metoclopramide without many of the adverse effects observed with parenteral administration of the drug. We performed a prospective, double‐blinded, randomized, placebo‐controlled study to evaluate the safety and efficacy of metoclopramide 20 mg administered intranasally for emetic prophylaxis in laparoscopic surgery patients. The results from 109 patients enrolled in the study showed that this intranasal dose of metoclopramide may be ineffective in preventing the occurrence of PONV The poor performance of the intranasal metoclopramide formulation in this study cannot be attributed to patient‐specific and perioperative factors. It may be due to an inadequate dose or slow absorption of the drug. The small sample size, however, may also have been a factor.