<zdoi;10.1097/ALN.0000000000000935> Anesthesiology, V 124 • No 2 270 February 2016 P RACTICE guidelines are systematically developed recommendations that assist the practitioner and patient in making decisions about health care. These recommendations may be adopted, modified, or rejected according to the clinical needs and constraints and are not intended to replace local institutional policies. In addition, practice guidelines developed by the American Society of Anesthesiologists (ASA) are not intended as standards or absolute requirements, and their use cannot guarantee any specific outcome. Practice guidelines are subject to revision as warranted by the evolution of medical knowledge, technology, and practice. They provide basic recommendations that are supported by a synthesis and analysis of the current literature, expert and practitioner opinion, open-forum commentary, and clinical feasibility data. This document updates the “Practice Guidelines for Obstetric Anesthesia: An Updated Report by the ASA Task Force on Obstetric Anesthesia,” adopted by ASA in 2006 and published in 2007.†

Practice Guidelines for Obstetric Anesthesia: An Updated Report by the American Society of Anesthesiologists Task Force on Obstetric Anesthesia and the Society for Obstetric Anesthesia and Perinatology ∗

Propofol is an intravenous sedative hypnotic agent which rapidly and reliably causes loss of consciousness. It is also associated with a quick and 'smooth' recovery, which distinguishes it from many of the more traditional anaesthetic regimens. Like other intravenous agents, propofol is both a cardiovascular and a respiratory depressant; however, the risk of these effects can be lessened by appropriate dosage adjustment or patient management. Anaphylaxis with propofol is rare. Propofol anaesthesia in day case surgery is consistently associated with a quicker early recovery than other intravenous agents and the more traditional anaesthetic regimens. Savings in time to discharge were more variable compared with these regimens, although propofol was commonly associated with less post-operative nausea and vomiting in this period. In the future, the relative benefits of propofol compared with the newer volatile agents (desflurane and sevoflurane) and propofol/volatile agent combinations need to be examined in this clinical setting. There is now clinical experience with propofol in major surgical procedures including cardiac and neurosurgery. Propofol has also been investigated as a sedative accompanying regional or local anaesthesia for diagnostic and therapeutic procedures, and in other clinical settings (ophthalmic surgery, cardioversion and electroconvulsive therapy). The unique antiemetic, antiepileptic and antipruritic effects of propofol may further broaden its appeal. As a result of its favourable recovery profile, propofol holds a central place in day case surgery anaesthesia. Accumulating clinical experience in cardiac and neurosurgery suggests that the full potential of propofol has yet to be realised.

Propofol. An update of its use in anaesthesia and conscious sedation.

Drugs administered to mothers have the potential to cross the placenta and reach the fetus. Under particular circumstances, the comparison of the drug concentration in the maternal and fetal plasma may give an idea of the exposure of the fetus to the maternally administered drugs. In this review drugs are classified according to their type of transfer across the placenta. Several drugs rapidly cross the placenta and pharmacologically significant concentrations equilibrate in maternal and fetal plasma. Their transfer is termed ‘complete’. Other drugs cross the placenta incompletely, and their concentrations are lower in the fetal than in maternal plasma. The majority of drugs fit into 1 of these 2 groups. A limited number of drugs reach greater concentrations in fetal than maternal plasma. It is said that these drugs have an ‘exceeding’ transfer. The impression prevails that suxamethonium chloride (succinylcholine chloride) and doxorubicin do not cross the placenta. However, a careful analysis of the literature suggests that this impression is wrong and that all drugs cross the placenta, although the extent transfer varies considerably. The following parameters were considered as possible factors determining the extent of placental transfer: (i) the molecular weight of the drug; (ii) the pKa (pH at which the drug is 50% ionised); and (iii) the extent of drug binding to the plasma protein. Drugs with molecular weights greater than 500D have an incomplete transfer across the human placenta. Strongly dissociated acid drug molecules should have an incomplete transfer, but this does not seem to be an absolute rule. For example, ampicillin and methicillin transfer completely and they are strongly dissociated at physiological pH. The extent of drug binding to plasma protein does not influence the type of drug transfer across the human placenta.

Placental Transfer of Drugs Administered to the Mother

Propofol is an intravenous hypnotic drug that is used for induction and maintenance of sedation and general anaesthesia. It exerts its effects through potentiation of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) at the GABAA receptor, and has gained widespread use due to its favourable drug effect profile. The main adverse effects are disturbances in cardiopulmonary physiology. Due to its narrow therapeutic margin, propofol should only be administered by practitioners trained and experienced in providing general anaesthesia. Many pharmacokinetic (PK) and pharmacodynamic (PD) models for propofol exist. Some are used to inform drug dosing guidelines, and some are also implemented in so-called target-controlled infusion devices, to calculate the infusion rates required for user-defined target plasma or effect-site concentrations. Most of the models were designed for use in a specific and well-defined patient category. However, models applicable in a more general population have recently been developed and published. The most recent example is the general purpose propofol model developed by Eleveld and colleagues. Retrospective predictive performance evaluations show that this model performs as well as, or even better than, PK models developed for specific populations, such as adults, children or the obese; however, prospective evaluation of the model is still required. Propofol undergoes extensive PK and PD interactions with both other hypnotic drugs and opioids. PD interactions are the most clinically significant, and, with other hypnotics, tend to be additive, whereas interactions with opioids tend to be highly synergistic. Response surface modelling provides a tool to gain understanding and explore these complex interactions. Visual displays illustrating the effect of these interactions in real time can aid clinicians in optimal drug dosing while minimizing adverse effects. In this review, we provide an overview of the PK and PD of propofol in order to refresh readers’ knowledge of its clinical applications, while discussing the main avenues of research where significant recent advances have been made.

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Clinical Pharmacokinetics and Pharmacodynamics of Propofol.

ANESTHESIA has become remarkably safe, and while death and permanent damage have become rare occurrences, other sequelae of anesthesia are gaining more importance. Postoperative nausea and vomiting (PONV) still is the most troublesome adverse event encountered in the recovery room, despite advances in prevention and treatment. The incidence of PONV has remained high and has a major negative impact on patient satisfaction about the overall surgical experience. Furthermore, the ongoing trend toward ambulatory procedures has increased the focus on PONV as its occurrence may delay discharge or cause unanticipated hospital admission. General anesthesia has long been considered as causing a greater frequency and severity of PONV than regional anesthetic techniques. Recent studies investigating this time-honored dictum in a controlled manner mostly, but not unanimously, confirmed it. Accordingly, considerable effort has been invested to examine etiology, define patients at risk, and outline preventive and therapeutic strategies in patients undergoing general anesthesia. Reviews dealing with PONV have discussed almost exclusively general anesthesia and largely ignored regional anesthesia. This contrasts with the increasing popularity of regional anesthesia. A survey in Europe showed that one third of patients are undergoing regional anesthesia for their operative procedure. In France, the proportion of regional anesthesia increased from 15 to 25% of all anesthetics administered from 1980 to 1996. The number of local anesthetic and analgesic agents available for regional anesthesia has increased over the last two decades. Since the introduction of intrathecal and epidural morphine in 1979, a multitude of medications, such as synthetic opioids, 2-agonists, and cholinesterase inhibitors, have been introduced in an attempt to enhance the action of local anesthetics. The decision about their usefulness will not only rely on their effects on nerve blockade and pain relief, but also on their influence on side effects such as PONV. This review focuses on PONV in the setting of perioperative regional anesthesia. General aspects of PONV, such as physiology, patient, and perioperative factors involved are discussed. Few studies regarding these issues have been specifically devoted to regional anesthesia. Therefore, much information must be derived from investigations of general anesthesia. Specific regional anesthetic techniques and the influence of adjunctive medications on PONV are also presented. Combined general–regional anesthesia is purposefully excluded, avoiding the many variables introduced by general anesthesia. A final section is devoted to continuous peripheral nerve blocks and their possible impact on PONV.

Postoperative nausea and vomiting in regional anesthesia: a review.

Placental transfer and neonatal effects of propofol were investigated in 21 women undergoing elective cesarean section under general anesthesia This study was conducted in two separate phases according to the use of propofol In both phases, anesthesia was induced with an iv bolus of 25 mg/kg of propofol In phase 1 (n = 10), anesthesia was maintained with 50% nitrous oxide in oxygen and halothane In phase 2 (n = 11), a continuous infusion of propofol at a rate of 5 mgkg-1h-1 was started after the induction dose Maternal venous and umbilical cord arterial and venous samples were obtained at delivery The propofol concentration in whole blood was measured with a high performance liquid chromatography method Where possible, breast milk/colostrum was expressed for both phases postoperatively and a sample of blood was collected during phase 2 from neonates via a heel prick 2 h after birth Propofol crossed the placenta, as demonstrated by concentrations found in umbilical venous blood in phase 1 (013-075 micrograms/ml) and in phase 2 (078-137 micrograms/ml) At delivery, the ratio of the drug concentration in umbilical venous blood to that in maternal blood was 070 +/- 006 for phase 1 and 076 +/- 010 for phase 2 The ratio of propofol concentration in the umbilical artery to that in the umbilical vein was 109 +/- 004 for phase 1 and 070 +/- 005 for phase 2(ABSTRACT TRUNCATED AT 250 WORDS)

Intravenous propofol during cesarean section: placental transfer, concentrations in breast milk, and neonatal effects. A preliminary study.

Placental transfer and neonatal effects of propofol were investigated in 21 women undergoing elective cesarean section under general anesthesia. This study was conducted in two separate phases according to the use of propofol. In both phases, anesthesia was induced with an iv bolus of 2.5 mg/kg of propofol. In phase 1 (n = 10), anesthesia was maintained with 50% nitrous oxide in oxygen and halothane. In phase 2 (n = 11), a continuous infusion of propofol at a rate of 5 mg.kg-1.h-1 was started after the induction dose. Maternal venous and umbilical cord arterial and venous samples were obtained at delivery. The propofol concentration in whole blood was measured with a high performance liquid chromatography method. Where possible, breast milk/colostrum was expressed for both phases postoperatively and a sample of blood was collected during phase 2 from neonates via a heel prick 2 h after birth. Propofol crossed the placenta, as demonstrated by concentrations found in umbilical venous blood in phase 1 (0.13-0.75 micrograms/ml) and in phase 2 (0.78-1.37 micrograms/ml). At delivery, the ratio of the drug concentration in umbilical venous blood to that in maternal blood was 0.70 +/- 0.06 for phase 1 and 0.76 +/- 0.10 for phase 2. The ratio of propofol concentration in the umbilical artery to that in the umbilical vein was 1.09 +/- 0.04 for phase 1 and 0.70 +/- 0.05 for phase 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Intravenous Propofol During Cesarean Section: Placental Transfer, Concentrations in Breast Milk, and Neonatal Effects. A Preliminary Study

Resume Un cas d'accident anaphylactique severe est rapporte, survenant chez une femme de 32 ans, apres extraction fœtale pratiquee par cesarienne sous rachianesthesie. L'agent declenchant est le latex des gants chirurgicaux, comme le prouvent les tests allergologiques : positivite des prick-tests au latex et du test de degranulation des basophiles humains, presence d'IgE specifiques du latex. Les tests pratiques avec les produits utilises pour l'anesthesie ont ete negatifs.

Choc anaphylactique peropératoire au latex

In a prospective, randomized double-blind study carried out on 255 parturients, fentanyl 80 μg (n = 81), morphine 4 mg (n = 83) or placebo (n = 85) was added to 0.25% bupivacaine administered extradurally for pain relief during labour. Fentanyl increased the mean duration of bupivacaine analgesia by 30% and did not reduce the rate of inadequate pain relief. Morphine did not increase the mean duration of bupivacaine analgesia significantly, but increased the rate of inadequate pain relief. It was concluded that morphine 4 mg added to extradural 0.25% bupivacaine was of no value.

Controlled trial of extradural bupivacaine with fentanyl, morphine or placebo for pain relief in labour

Resume Dans une etude realisee en double insu, chez 124 parturientes devant beneficier d'une analgesie peridurale en debut de travail, il a ete associe a 12 ml de bupivacaine a 0,25 % non adrenalinee, respectivement 15 μg de sufentanil, 75 μg de fentanyl ou 2 ml de chlorure de sodium a 9 ‰. L'etude a montre que l'adjonction de 15 μg de sufentanil augmente de maniere significative (22 %) la duree de l'analgesie de la bupivacaine et celle-ci est comparable a celle obtenue avec 75 μg de fentanyl. Aucun effet indesirable n'a ete constate chez le fœtus et le nouveau-ne. Le prurit, comme habituellement decrit, a ete le seul effet secondaire releve de maniere identique dans les deux groupes morphiniques.

J. C. Jorrot

Papers

Intravenous propofol during cesarean section: placental transfer, concentrations in breast milk, and neonatal effects. A preliminary study.

Intravenous Propofol During Cesarean Section: Placental Transfer, Concentrations in Breast Milk, and Neonatal Effects. A Preliminary Study

Choc anaphylactique peropératoire au latex

Controlled trial of extradural bupivacaine with fentanyl, morphine or placebo for pain relief in labour

Association sufentanil-bupivacaïne à 0,25 % par voie péridurale pour l'analgésie obstétricale. Comparaison avec le fentanyl et un placebo