PubMed HealthSearch

Biomedical subjects

B K Wagner

Publications and source records attributed to B K Wagner.

At least 19 recordsLinked to original sources

Pharmacokinetics and pharmacodynamics of sedatives and analgesics in the treatment of agitated critically ill patients.

The 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.

Analgesics

Drugs for amnesia in the ICU.

OBJECTIVE: This review focuses on how patients' recall of their stay in the ICU can be modified pharmacologically. DATA SOURCES: Computerized MEDLINE and PAPERCHASE searches of English- and foreign-language published research from 1966 to 1995, bibliographies, pharmaceutical and personal files, and conference abstract reports. STUDY SELECTION: All abstracts from uncontrolled and controlled clinical trials were reviewed. DATA EXTRACTION: Study design, population, results, and safety information were retained. Efficacy conclusions were drawn from controlled trials. DATA SYNTHESIS: Patients without cerebral injury may recall mental and physical discomfort during their stay in the ICU. All benzodiazepines produce amnestic effects, but the short duration of action, lack of long-acting metabolites, and potent amnestic effects make lorazepam and midazolam preferable in this setting. Infusions of propofol for conscious sedation produce concentrations below those required for consistent amnesia. Opioids generally do not produce amnesia; however, end-organ failure and use of high doses of opioids may increase plasma concentrations to levels that produce impairment of learning and various degrees of amnesia. High infusion rates of ketamine may be required for satisfactory amnesia and pain control (with coadministration of benzodiazepine). Barbiturates and haloperidol do not impair memory in patients who are not critically ill. Antihistamines and anticholinergics that do not penetrate the central nervous system do not produce amnesia. Flumazenil may induce recall. CONCLUSIONS: Patients may remember their stay in the ICU, depending on the type of injury and the drug therapy. Of the drugs presented, benzodiazepines most reliably provide anterograde amnesia, whereas ketamine and propofol exhibit dose-dependent effects on memory.

Aged

Comparison of intranasal midazolam and sufentanil premedication in pediatric outpatients.

BACKGROUND: Intranasally administered midazolam was compared with sufentanil as a premedicant for 60 patients, aged 1/2 to 6 years, undergoing outpatient surgery of 2 hours or less. METHODS: Thirty minutes before anesthetic induction (halothane in 50% nitrous oxide/oxygen), patients were randomly assigned to receive either intranasal midazolam (0.2 mg/kg) or sufentanil (2 microg/kg). A "blinded" observer evaluated preoperative emotional state, response to premedication, induction, and emergence from anesthesia and side effects. RESULTS: Children who had not previously cried were more likely to cry when midazolam was administered compared with sufentanil (71% versus 20%, p = 0.0031). Of 31 midazolam patients, 20 experienced nasal irritation. Approximately 15 to 20 minutes after drug administration, most patients in both groups could be comfortably separated from their parents. The sufentanil group appeared to be more sedated and more cooperative during induction of anesthesia. Vital signs and oxygen saturation did not change significantly with either medication before or after surgery, although two sufentanil patients had a moderate reduction in ventilatory compliance after anesthetic induction. Sufentanil was associated with more nausea and vomiting than midazolam (34% versus 6%, p < 0.02). CONCLUSION: Both intranasal midazolam and sufentanil provide rapid, safe, and effective sedation in small children before anesthesia for ambulatory surgery. Sufentanil provided somewhat better conditions for induction and emergence. Midazolam causes more nasal irritation during instillation, and sufentanil causes more postoperative nausea and vomiting. Both drugs enabled patients to be separated from their parents with a minimum of distress. Patients in the midazolam group were discharged approximately 40 minutes earlier (p <0.005).

Adjuvants, Anesthesia

A tau promoter region without neuronal specificity.

The microtubule-associated protein tau is produced from a 6-kb mRNA expressed primarily in neurons. A 2-kb tau mRNA has also been characterized, which produces a tau isoform that localizes to the nucleus, and an 8-kb mRNA is expressed in the PNS. Mapping and sequencing of the human tau gene start showed that it has an unusually GC-rich 5'-untranslated region coded by a single untranslated exon (designated -1). Primer extensions and expression assays indicated that upstream of exon -1 is a promoter that is not neuron specific. This region contains consensus binding sites for transcription factors AP2, Sp1, and GCF.

Base Sequence

Aprotinin.

OBJECTIVE: To review the clinical pharmacology of aprotinin in patients undergoing surgical procedures involving major blood loss, namely, coronary artery bypass graft (CABG). DATA SOURCES: A MEDLINE search was used to identify French- and English-language publications on aprotinin using the indexing terms aprotinin, cardiothoracic surgery, and hemorrhage. The MEDLINE search was supplemented by review of article bibliographies. Data also were obtained from the approved Canadian and US product labels. STUDY SELECTIONS: All abstracts and uncontrolled and controlled clinical trials were reviewed. DATA EXTRACTION: Study design, population, results, and safety information were retained. Efficacy conclusions were drawn from controlled trials. DATA SYNTHESIS: Aprotinin, a serine protease inhibitor isolated from bovine lung tissue, decreases bleeding after cardiac surgery by mechanisms including antifibrinolytic activity and preservation of platelet function. Several trials have shown that aprotinin reduced blood loss and transfusion requirements in patients undergoing CABG. Its use in other surgical procedures involving major blood loss has been reported. Aprotinin is well tolerated, with minor allergic reactions being the most frequently reported adverse effect. Although unsubstantiated, the possibility that aprotinin could create a prothrombic state leading to early graft occlusion and formation of microthrombi in renal and coronary vasculatures is of concern. CONCLUSIONS: Aprotinin is an effective hemostatic agent in CABG. Clear definitions of indications, dosing, safety, and repeated use remain to be investigated thoroughly.

Aprotinin

Use of patient-controlled analgesia with alfentanil for extracorporeal shock wave lithotripsy.

STUDY OBJECTIVE: To compare the efficacy of patient-controlled analgesia (PCA) to physician-controlled analgesia in patients undergoing extracorporeal shock wave lithotripsy (ESWL). DESIGN: Prospective, randomized trial. SETTING: New Jersey Kidney Stone Treatment Center at Robert Wood Johnson University Hospital, New Brunswick, NJ. PATIENTS: 62 ASA I, II, and III patients undergoing ESWL. INTERVENTIONS: The control group (n = 29) received physician-controlled analgesia with continuous infusions (0.75 mcg/kg/min) and intermittent boluses (5 mcg/kg) of alfentanil. PCA patients (n = 33) initially received alfentanil 0.5 mcg/kg followed by a continuous background infusion (0.2 to 0.5 mcg/kg/min) and self-administered alfentanil (3 to 5 mcg/kg) with a 5-minute lockout period. Bolus doses and infusion rates were determined by patient comfort and cardiorespiratory response to alfentanil. MEASUREMENTS AND MAIN RESULTS: Prior to the procedure, the patients completed two questionnaires (State-Trait Anxiety Inventory and Multidimensional Health Locus of Control Scales). During ESWL, blood pressure, heart rate, respiratory rate, oxygen saturation, end-tidal CO2, and pain and sedation levels were measured at 0, 800, 1,600, 2,400, and 3,000 shock waves. The total doses of alfentanil administered were calculated. PCA patients received 31% less alfentanil than control group patients (p < 0.0001). Patients with more preoperative anxiety required larger doses of alfentanil (p < 0.05). The pain level was slightly higher in the patients receiving PCA (p > 0.05) but most patients reported either no or only mild pain. Side effects from the therapy, such as nausea and vomiting, were either not present or were mild in both groups, with one patient (3% to 4%) in each group reporting mild nausea. Both patients and urologists were very satisfied with the pain management in both groups. CONCLUSIONS: PCA is a useful alternative to physician-controlled analgesia during ESWL since it provides equivalent pain control while using less alfentanil.

Adult

Pharmacological interventions for agitation in head-injured patients in the acute care setting.

Agitation following head injury challenges nurses to provide patient safety and participation in daily care and therapies. Diagnosis of the underlying disorder which causes agitative behavior is essential for rapid and successful treatment. A combination of pharmacological and nonpharmacological interventions are required to achieve this expected outcome. Propofol, lorazepam, midazolam and haloperidol are medications most commonly utilized in this patient care situation. The patient's sedation level should be monitored to avoid oversedation which may interfere with respiration and neurological status. Nurses need to understand the actions and adverse effects of these agents in order to advocate their proper usage in the agitated head-injured population.

Adult

Effects of intravenous famotidine on gastric acid secretion in patients undergoing cardiac surgery.

OBJECTIVE: To determine the effects of cardiopulmonary bypass and famotidine on gastric acid secretion in adults undergoing cardiac surgery. DESIGN: Prospective, randomized, double-blind, placebo-controlled study. SETTING: University teaching hospital. PARTICIPANTS: Eighteen patients undergoing elective cardiac surgery with cardiopulmonary bypass. MAIN OUTCOME MEASURES: Famotidine 20 mg or NaCl 0.9% placebo was administered intravenously following induction of anesthesia and placement of a nasogastric pH probe. A second dose was given 12 hours after surgery in the intensive care unit. Gastric pH was measured continuously and gastric volume was measured every 4 hours for up to 24 hours after cardiopulmonary bypass. RESULTS: Following famotidine administration, pH increased by 43% within 45 minutes and remained above 5.5 throughout the study period (p < 0.05 vs placebo and baseline). The gastric pH did not increase, but remained above 4.0 in most patients in the placebo group for up to 12 hours after cardiopulmonary bypass. Gastric volumes were on average 24% lower in the famotidine group (p > 0.05). CONCLUSIONS: Gastric acid secretion is decreased during and for 12 hours after cardiopulmonary bypass. Perioperative administration of famotidine suppresses gastric secretion in cardiac surgery patients.

Adult

Use of vitamin B12 in the treatment and prevention of nitroprusside-induced cyanide toxicity.

OBJECTIVE: To review the mechanism of action, safety, and efficacy of hydroxocobalamin in the treatment and prevention of nitroprusside-induced cyanide toxicity. DATA SOURCES: English and foreign-language journal articles and reference texts identified from Index Medicus. Both animal and human studies were included. DATA SYNTHESIS: High-dose or prolonged therapy with nitroprusside in patients with hepatic or renal dysfunction increases the risk for nitroprusside-induced cyanide or thiocyanate toxicity, respectively. Hydroxocobalamin has been shown to significantly reduce RBC and plasma cyanide concentrations in animals and surgical patients without producing clinically important adverse effects or toxic metabolites. Thiosulfate infusions also decrease cyanide toxicity but can cause accumulation of thiocyanate resulting in clinical toxicity. Cyanocobalamin cannot effectively remove cyanide due to poor binding. CONCLUSIONS: Hydroxocobalamin is a safe and effective agent in the prevention and treatment of nitroprusside-induced cyanide toxicity. Prolonged or high-dose infusions of nitroprusside should be minimized in critically ill patients, especially if hepatic and/or renal dysfunction is present.

Animals

Pharmacologic and clinical considerations in selecting crystalloid, colloidal, and oxygen-carrying resuscitation fluids, Part 1.

The pharmacologic properties of crystalloid, colloidal, and oxygen-carrying resuscitation fluids are described, and the findings of clinical trials of these solutions are discussed. Fluid administration is a fundamental part of resuscitation therapy. Crystalloid solutions supply water and sodium to maintain the osmotic gradient between the extravascular and intravascular compartments. Examples are lactated Ringer's injection and 0.9% sodium chloride injection. Colloidal solutions, such as those containing albumin, dextrans, or starches, increase the plasma oncotic pressure and effectively move fluid from the interstitial compartment to the plasma compartment. Oxygen-carrying resuscitation fluids, such as whole blood and artificial hemoglobin solutions, not only increase plasma volume but improve tissue oxygenation. Clinically, colloidal solutions are generally superior to crystalloids in their ability to expand plasma volume. However, colloids may impair coagulation, interfere with organ function, and cause anaphylactoid reactions. Crystalloid solutions represent the least expensive option and are less likely to promote bleeding, but they are more likely to cause edema because larger volumes are needed. Favorable experience with inexpensive hypertonic crystalloids with improved plasma volume expansion properties may favor a return to resuscitation with crystalloid solutions. Oxygen-carrying resuscitation fluids are indicated when the patient has lost more than 25% of the total blood volume. Tailoring therapy to the individual patient and close monitoring are essential to safe and effective fluid resuscitation.

Colloids

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 Coomb's 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.

Anemia, Hemolytic

Use of a continuous alfentanil infusion for extracorporeal shock wave lithotripsy in the treatment of renal calculi.

Extracorporeal shock wave lithotripsy (ESWL) is the most widely used treatment for renal calculi. Newer second generation lithotripters are being produced, which are considered to be less painful than their prototypes. Thus, the trend in anesthesia for ESWL is away from general endotracheal and regional anesthesia and toward less involved and more easily monitored techniques such as intravenous analgesia (IVA). This report relates our experience with a continuous alfentanil infusion for ESWL treatment of renal calculi with a nonimmersion second generation Dornier HM-4 lithotripter model. Thirty-five patients treated pre-operatively with droperidol and midazolam, followed by a continuous infusion of alfentanil, reported excellent pain relief via a numerical pain score and manifested little, if any, hypertension or tachycardia. Stone fragmentation, fluoroscopy, and recovery time did not differ between patients receiving IVA or general anesthesia. Potential disadvantages of IVA include elevation of transcutaneous CO 2, bradycardia in 14 patients requiring the use of atropine, slightly longer ESWL time, increased number of shocks needed for fragmentation, and a small failure rate, with 11% of patients requiring general anesthesia. With proper patient selection and respiratory monitoring, IVA is highly recommended for ESWL in the treatment of renal calculi.

Adult

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

Adult

Hemodynamic effects of intravenous famotidine in patients undergoing cardiac surgery.

STUDY OBJECTIVE: To determine the hemodynamic effects of famotidine in patients undergoing cardiac surgery. DESIGN: A prospective, randomized, double-blinded, placebo-controlled study. SETTING: A large university teaching hospital. PATIENTS: Twenty-one patients undergoing elective cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: The patients received a rapid intravenous bolus injection of famotidine 20 mg or saline placebo after anesthesia induction. A second dose was given 12 hours after surgery in the intensive care unit. MEASUREMENTS AND MAIN RESULTS: Serial hemodynamic measurements (heart rate, arterial blood pressure, cardiac index, pulmonary arterial pressure, central venous pressure, systemic vascular resistance) were obtained after each famotidine or placebo dose and analyzed by ANOVA: The values were not altered (p > 0.05) after intraoperative or postoperative famotidine or placebo administration. CONCLUSIONS: Rapid intravenous bolus administration of famotidine does not alter patient hemodynamics after anesthesia induction or in the intensive care unit after cardiac surgery.

Aged

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.

Antiemetics

Faculty have few incentives for becoming board certified in pharmacotherapy.

A telephone survey of all colleges of pharmacy in the United States (including Puerto Rico) and Canada was conducted to assess the incentives offered for pharmacy practice faculty to become board-certified pharmacotherapy specialists (BCPS). Board certification is not a requirement for employment at any college of pharmacy; however, it plays a part in promotion, tenure, and merit salary increases at several schools. Fewer than half of the schools provide at least partial reimbursement of examination-related expenses. Sixteen have initiated BCPS study groups. We perceive that faculty must have more incentives to take the examination. It may be difficult to change institutional policies regarding merit increases or promotion and tenure, but colleges of pharmacy can do more to decrease the cost burden and to promote study groups within the department.

Canada