Anesthesiology. First of two parts.

Spinal anaesthesia developed in the late 1800s with the work of Wynter, Quincke and Corning. However, it was the German surgeon, Karl August Bier in 1898, who probably gave the first spinal anaesthetic. Bier also gained first-hand experience of the disabling headache related to dural puncture. He correctly surmised that the headache was related to excessive loss of cerebrospinal fluid (CSF). In the last 50 yr, the development of fine-gauge spinal needles and needle tip modification, has enabled a significant reduction in the incidence of post-dural puncture headache. Though it is clear that reducing the size of the dural perforation reduces the loss of CSF, there are many areas regarding the pathogenesis, treatment and prevention of post-dural puncture headache that remain contentious. How does the microscopic pattern of collagen alignment in the spinal dura affect the dimensions of the dural perforation? How do needle design, size and orientation influence leakage of CSF through the dural perforation? Can pharmacological methods reduce the symptoms of post-dural puncture headache? By which mechanism does the epidural blood patch cure headache? Is there a role for the prophylactic epidural blood patch? Do epidural saline, dextran, opioids and tissue glues reduce the rate of CSF loss? This review considers these contentious aspects of post-dural puncture headache.

Post‐dural puncture headache: pathogenesis, prevention and treatment

Drug research encompasses several diverse disciplines united by a common goal, namely the development of novel therapeutic agents. The search for new drugs can be divided functionally into two stages: discovery and development. The former consists of setting up a working hypothesis of the target

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Role of Pharmacokinetics and Metabolism in Drug Discovery and Development

Background:Target-controlled infusion is an increasingly common type of administration for propofol. This method requires accurate knowledge of pharmacokinetics, including the effects of age and weight. The authors performed a multicenter population analysis to quantitate the effects of covariates.M

Population pharmacokinetics of propofol: a multicenter study.

https://escholarship.org/content/qt8xh0s7nf/qt8xh0s7nf.pdf?t=oyg19p

Fentanyl, fentanyl analogs and novel synthetic opioids: A comprehensive review

Because of remifentanil's unique pharmacokinetics, its systemic administration may be suitable for clinical settings where a potent, fast-acting, systemic mu-opioid with a rapid recovery is required, e.g., short painful intervention in the emergency room or the intensive care unit, or procedures in the day surgery or endoscopy suite. Total intravenous anesthesia for longer lasting procedures may become more promising because of the predictability of the offset of remifentanil even after long infusions. Its closest competitor, alfentanil, depends on its small volume of distribution for rapid termination of its effect, but still possesses the potential to accumulate because of its relatively long terminal elimination half-life. Remifentanil might be the first potent mu-opioid that does not accumulate in this fashion, and therefore it opens promising new clinical perspectives (52). However, as mentioned above, the relative short-lasting analgesic effect after cessation of the remifentanil infusion might require new, sophisticated techniques from the anesthetist to prevent immediate onset of postoperative pain.

Remifentanil: a novel, short-acting, mu-opioid.

T he evolution of obstetric anesthesia and analgesia has closely followed anesthesia for other subspecialties. In 1847, shortly after the first public demonstration of ether anesthesia for general surgery, James Young Simpson used diethyl ether for labor analgesia (1). Other methods followed, such as repeated injections of large doses of morphine and scopolamine. This technique, called “Dämmerschlaf” or “twilight sleep,” often led to severe maternal and neonatal respiratory depression (2). During the initial enthusiasm for alleviating maternal discomfort, proponents of obstetric analgesia gave little thought to the neonatal effects of maternal drug administration. This was, in part, because successful labor and delivery were essentially defined in terms of maternal and fetal survival, rather than physiological variables of the newborn. In 1847, Walter Channing stated that placental transfer of ether was negligible, as he could not detect an odor of ether after having cut the umbilical cord (3). Although the significance of placental drug transfer was recognized in 1877 when Paul Zweifel proved the presence of chloroform in umbilical vessels of newborns, this knowledge did not alter clinical practice over the next decades. One hundred years ago, in July 1900, the obstetrician Oscar Kreis, from Switzerland was the first to recognize the advantages of regional analgesia in obstetrics, when applying spinal cocaine to ameliorate labor pain in six parturients with a fully dilated cervix (4). Although the neonatal status was not mentioned, Kreis described the parturients as remarkably alert compared with women who received other available forms of labor analgesia. Major side effects in those early cases included a high incidence of postdural puncture headaches (PDPH) and vomiting, which occurred in half of the patients. In 1902, Hopkins subsequently performed the first cesarean delivery under spinal anesthesia in the United States. As early as 1923, the first reports on combined spinal-epidural anesthetics (CSE) in surgical patients appeared, initially as a combined single-shot technique (5). The basis of regional blocks for labor analgesia was founded on neuroanatomical principles, when Cleland (6) described the sensory innervation of the uterus in 1933. The following frequent use of spinal anesthesia by inexperienced personnel and the perception that monitoring was not necessary led to a frequent incidence of complications and brought discredit to the technique. At the time, mortality after spinal anesthesia was 1 in 1000 in surgical patients, a rate much more frequent than those observed for either local or general anesthesia (7). Mortality rates for cesarean deliveries performed under spinal anesthesia were reported to be 1 in 139 (8). Greenhill (9), engaged in obstetric anesthesia, therefore concluded that spinal anesthesia was the most dangerous of all forms of anesthesia for pregnant women. He repeatedly discouraged its use in obstetrics. The negative experiences with regional anesthesia resulted in an abandonment of pain relief in obstetrics until the 1950s, a period often described as the “dark ages of obstetric anesthesia” (1). It was during this time that “natural childbirth” and “psychoprophylaxis” were widely advocated to avoid serious anesthesia-related side effects (10). Major improvements in maternal safety were made between 1940 and 1950, when 24-hour obstetric anesthesia services were established throughout the United States. The first experiences with caudal anesthesia in obstetrics suggested that this technique might enhance safety for the parturient and the fetus, and it provided good labor pain relief (11). Parturients were more willing to accept caudal anesthesia than subarachnoid injections, as the high risk of PDPH was publicly known. In the following years, lumbar epidural analgesia gained more popularity because the success rate was more frequent, local anesthetic requirements were reduced, the onset of analgesia was faster, and the catheter was positioned in a place considered less prone for infection (12). Although the first cases of continuous lumbar epidural anesthesia were Accepted for publication June 13, 2000. Address correspondence and reprint requests to H. Van Aken, MD, PhD, FRCA, FANZCA, Klinik und Poliklinik für Anästhesiologie und operative Intensivmedizin, Westfälische Wilhelms-Universität, AlbertSchweitzer-Str. 33, D-48149 Münster, Germany. Address e-mail to hva@anit.uni-muenster.de.

A century of regional analgesia in obstetrics.

Volatile anesthetics exert a protective role in myocardial ischemia. An increase in sympathetic tone might exert deleterious effects on the ischemic myocardium. The use of the volatile anesthetic desflurane in myocardial ischemia is controversial because of its sympathetic activation. We compared propofol and desflurane on myocardial stunning in chronically instrumented dogs. Mongrel dogs (n = 8) were chronically instrumented for measurement of heart rate, left atrial, aortic, and left ventricular pressure, rate of rise of left ventricular pressure, and myocardial wall-thickening fraction (WTF). An occluder around the left anterior descending artery (LAD) allowed the induction of reversible LAD-ischemia. Two experiments were performed in a cross-over fashion on separate days: 1) Induction of 10 min of LAD-ischemia during desflurane anesthesia and 2) Induction of 10 min of LAD-ischemia during propofol anesthesia. Both anesthetics were discontinued immediately after completion of ischemia. WTF was measured at predetermined time points until complete recovery from ischemic dysfunction occurred. Both anesthetics caused a significant decrease of WTF in the LAD-perfused myocardium. LAD-ischemia led to a further significant decrease of LAD-WTF in both groups. During the first 3 h of reperfusion, WTF was significantly larger in the desflurane group. Mean arterial pressure and heart rate were greater during ischemia and the first 10 min of reperfusion in the desflurane group compared with the propofol group. Recovery from myocardial stunning in dogs was faster when desflurane was used at the time of ischemia as compared with propofol anesthesia. The mechanism for this difference is unclear, but sympathetic activation by desflurane was not a limiting factor for ischemic tolerance in chronically instrumented dogs.

Recovery from myocardial stunning is faster with desflurane compared with propofol in chronically instrumented dogs.

Increasing the inspiratory concentration of isoflurane is a commonly used technique for producing deliberate hypotension (DH) when isoflurane is used as the principal anesthetic. When an intravenous anesthetic technique is used, DH can be produced by the administration of a peripheral vasodilator, eventually in association with low concentrations of isoflurane. The aim of this investigation was to compare the effects of these two different approaches on vital organ blood flow. DH was induced in 12 mongrel dogs with two different anesthetic techniques: inhaled anesthesia with isoflurane (ISO) or an intravenous anesthetic technique combining propofol and alfentanil in combination with the α-adrenoreceptor antagonist, urapidil, and isoflurane at low end-expiratory concentrations. Mean arterial pressure (MAP) was initially decreased by 20% of its baseline and then to 50 mm Hg. Vital organ blood flows and the cerebral metabolic rate for oxygen were determined at each decrement in MAP, and after discontinuation of DH. A decrease in cardiac output was observed in the ISO group when MAP was decreased to 50 mm Hg. Cerebral blood flow was constantly and significantly higher in the ISO group. The cerebral metabolic rate for oxygen did not change compared to baseline values in both groups. At a MAP of 50 mm Hg, a decrease in renal blood flow was observed in both groups. Splanchnic blood flow remained stable in the intravenous anesthetic group in contrast to the ISO group where splanchnic blood flow decreased significantly. The combination of total intravenous anesthesia, urapidil, and low inspired concentrations of isoflurane to produce DH may be preferable to high concentrations of isoflurane, because cerebral hyperemia is avoided and splanchnic blood flow is better preserved.

Vital organ blood flow during deliberate hypotension in dogs.

The blood concentrations of propofol have been examined during anesthesia by continuous infusion of 12 mg/hg/hr. A bolus dose of 3 mg/kg body weight propofol was used to induce anesthesia. The mean concentrations at apparent steady state were in the range of 4.3 to 5.6 micrograms/ml during the infusion. The mean total body clearance, derived from the apparent steady state concentrations in the blood, was 0.0394 litres/kg/minute. The mean propofol blood concentration at awakening was found to be 2.3 micrograms/ml.

Van Aken H

Papers

Remifentanil: a novel, short-acting, mu-opioid.

A century of regional analgesia in obstetrics.

Recovery from myocardial stunning is faster with desflurane compared with propofol in chronically instrumented dogs.

Vital organ blood flow during deliberate hypotension in dogs.

Pharmacokinetics of propofol during continuous infusion for pediatric anesthesia.