Pharmacokinetics of midazolam, propofol, and fentanyl transfer to human breast milk.

BACKGROUND AND OBJECTIVES: Lactating women undergoing operations requiring general anesthesia are advised to pump and discard their milk for 24 hours after the procedure. Data on anesthetic drug transfer into breast milk are limited. This study determined the pharmacokinetics of midazolam, propofol, and fentanyl transfer into milk to provide caregivers with data regarding the safety of breast milk after administration of these drugs. METHODS: Five lactating women participated in this study after providing institutionally approved written informed consent. Patients underwent premedication with midazolam before induction of anesthesia with propofol and fentanyl. Anesthesia was maintained with a potent volatile anesthetic. Milk and blood were collected before drug administration. Milk was collected 5, 7, 9, 11, and 24 hours after drug administration. Venous blood was collected at intervals up to 7 hours. Plasma and milk midazolam, propofol, and fentanyl concentrations were measured by HPLC with tandem mass spectrometric or fluorescence detection. The pharmacokinetics of drug transfer into milk was modeled with plasma pharmacokinetics. RESULTS: Plasma midazolam, propofol, and fentanyl pharmacokinetics were consistent with reports of others. In 24 hours of milk collection, averages of 0.005% (range, 0.002%-0.013%) of the maternal midazolam dose, 0.027% (0.004%-0.082%) of the propofol dose, and 0.033% (0.006%-0.073%) of the fentanyl dose were collected in milk, representing averages of 0.009%, 0.025%, and 0.039% of the respective elimination clearances. CONCLUSION: The amount of midazolam, propofol, and fentanyl excreted into milk within 24 hours of induction of anesthesia provides insufficient justification for interrupting breast-feeding.

Retrograde autologous priming of the cardiopulmonary bypass circuit: safety and impact on postoperative outcomes.

OBJECTIVES: Retrograde autologous priming (RAP) is a blood conservation technique used to limit the severity of hemodilution during cardiopulmonary bypass and reduce perioperative transfusions. The aim of this investigation was to examine the safety of RAP and to determine the effect of RAP on adverse outcomes after cardiac surgery. DESIGN: Retrospective cohort study. SETTING: University hospital. PARTICIPANTS: Five hundred fifty-nine undergoing cardiopulmonary bypass. INTERVENTIONS: Data were retrospectively collected on 2 cohorts of adult cardiac surgical patients operated on by a single surgeon. In the RAP group (n = 256), outcome data were analyzed on all subjects over a 2-year period during which RAP was used routinely. This group was compared with a similar cohort of patients undergoing cardiopulmonary bypass over a 2-year period immediately before the introduction of RAP into the clinical practice (no-RAP group, n = 287). MEASUREMENTS AND MAIN RESULTS: In-hospital mortality was not significantly different between the RAP group (2.7%) and the no-RAP group (3.8%, p = 0.636). The incidence of postoperative cardiac arrest was significantly less in the RAP group (1 patient) compared to the no-RAP group (9 patients, p = 0.040). There were no differences between the 2 groups in the incidence of several other postoperative complications, including postoperative delirium (1.6% RAP v 3.1% no RAP), heart block (1.6% RAP v 4.2% no RAP), atrial fibrillation (19.1% RAP v 22.7% no RAP), and requiring postoperative ventilation >24 hours (2.7% RAP v 5.2% no RAP). CONCLUSIONS: The authors observed no evidence of any increase in adverse events in the RAP group of this retrospective cohort study, but they did observe a decrease in the incidence of postoperative cardiac arrest in the RAP group. These findings suggest that RAP is a safe technique and may have a beneficial effect on postoperative outcomes.

Is the pulmonary artery catheter useful?

In the United States more than 1.5 million pulmonary artery catheters (PACs) are inserted each year. Of these, approximately 55% are placed in high-risk surgical and trauma patients. Most clinicians believe that PAC use is beneficial in guiding therapy and may improve outcome. Despite these beliefs and hundreds of published articles related to PACs, appropriate use and impact on outcome remain unclear. A review of the current literature reveals conflicting data and significant flaws in most study designs. Inadequate sample size, lack of randomization, lack of standardization of therapies to PAC data, and deficiencies in user knowledge all significantly limit interpretation of clinical trials. Despite these deficiencies and the need for better-designed investigations, it is the opinion of the authors that access to hemodynamic data provided by the PAC, coupled with accurate interpretation of the data, may lead to reduced perioperative morbidity and mortality.

Sedation, analgesia, and neuromuscular blockade in sepsis: an evidence-based review.

OBJECTIVE: In 2003, critical care and infectious disease experts representing 11 international organizations developed management guidelines for sedation, analgesia, and neuromuscular blockade in sepsis that would be of practical use for the bedside clinician, under the auspices of the Surviving Sepsis Campaign, an international effort to increase awareness and improve outcome in severe sepsis. DESIGN: The process included a modified Delphi method, a consensus conference, several subsequent smaller meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. METHODS: The modified Delphi methodology used for grading recommendations built on a 2001 publication sponsored by the International Sepsis Forum. We undertook a systematic review of the literature graded along five levels to create recommendation grades from A to E, with A being the highest grade. Pediatric considerations to contrast adult and pediatric management are in the article by Parker et al. on p. S591. CONCLUSION: There is no preferred sedative or analgesic agent for use in the critically ill septic patient during mechanical ventilation. Protocols should be utilized for administration of sedation with predefined sedation scale targets. Either intermittent bolus sedation or continuous infusion sedation to predetermined end points with daily interruption/lightening of continuous infusion sedation with awakening and re-titration, if necessary, are recommended. Neuromuscular blockade should be avoided if possible and, if used continuously, requires twitch monitoring.

The failure of retrograde autologous priming of the cardiopulmonary bypass circuit to reduce blood use after cardiac surgical procedures.

UNLABELLED: Hemodilution during cardiopulmonary bypass (CPB) is a primary risk factor for blood transfusion in cardiac surgical patients. Priming of the CPB circuit with the patients' own blood (retrograde autologous priming, RAP) is a technique used to limit hemodilution and reduce transfusion requirements. We designed this study to examine the impact of RAP on perioperative blood product use. Using a retrospective cohort study design, the medical records of all patients undergoing CPB (excluding circulatory arrest cases) by a single surgeon were examined. Data were collected over a 24-mo period when RAP was routinely used as a blood conservation strategy (RAP group, n = 257). This group was compared with a cohort of patients during the 24 mo immediately preceding the introduction of RAP into clinical practice (no RAP group, n = 288). A small, statistically insignificant reduction in the percentage of patients receiving packed red blood cells was observed in the RAP group (44% versus 51% no RAP, P = 0.083). No differences were found between the groups in the number of units of packed red blood cells, platelets, or fresh frozen plasma transfused throughout the perioperative period. These results suggest that overall, RAP does not offer a clinically important benefit as a blood conservation technique. IMPLICATIONS: Priming of the cardiopulmonary bypass circuit with the patients' own blood (retrograde autologous priming) resulted in insignificant reductions in blood use in a large, unselected group of patients undergoing cardiac surgical procedures.

Gene therapy in heart and lung disease.

PURPOSE OF REVIEW: Gene therapy utilizes viral and non-viral vectors to transfer genetic material into a host in the hope of treating disease. This article will review the potential applications of gene therapy in the treatment of cardiac and pulmonary diseases. RECENT FINDINGS: The results from several phase I and II clinical trials have recently been published. In patients with ischemic heart disease, evidence of coronary revascularization has been observed after the delivery of angiogenic factors. Several trials have demonstrated a reduction in anginal symptoms, increases in exercise tolerance, and objective improvements in myocardial perfusion. Evidence of the transfer of therapeutic genes has been observed in human trials of inherited pulmonary diseases. Unfortunately, there has been little evidence of clinical efficacy in these studies. A variety of gene therapy strategies are being explored in the treatment of thoracic malignancies. Partial antitumor responses have occurred in some of the subjects enrolled in these studies. SUMMARY: Significant progress has been made in the field of gene therapy in the past decade. Data from these early animal and human clinical trials will provide important information to guide future studies.

Declining proportion of publications by American authors in major anesthesiology journals.

A decline in the proportion of articles published by American authors in medical journals has been reported. We therefore sought to determine whether the contributions of authors from the United States to the three leading anesthesia journals changed between the years 1980 to 2000. The journals Pain, Anesthesiology, and Anesthesia & Analgesia were selected for evaluation on the basis of their respective impact factors. All clinical studies and basic science studies published in the years 1980, 1985, 1990, 1995, and 2000 were evaluated. The country of origin of the lead author of each article was determined by two of the investigators. chi(2) Tests and least squares linear regression analyses were used to determine associations between the source of publication (United States or abroad) and year of publication. The proportion of American publications in the leading anesthesia specialty journals was found to be decreasing over the period 1980-2000 because of an increase in the rate of publication from abroad that is disproportionate to the increase in the total number of publications in the journals over that time. The reasons for changes in anesthesia-related publications by American authors were not established by this study. The authors speculate that multiple factors are involved, including an increased emphasis on clinical care over research because of economic constraints, American publication in journals other than the leading specialty journals, and the increased quality of submissions from abroad.