In utero Exposure to Anesthetics Alters Neuronal Migration Pattern in Developing Cerebral Cortex and Causes Postnatal Behavioral Deficits in Rats.

During fetal development, cerebral cortical neurons are generated in the proliferative zone along the ventricles and then migrate to their final positions. To examine the impact of in utero exposure to anesthetics on neuronal migration, we injected pregnant rats with bromodeoxyuridine to label fetal neurons generated at embryonic Day (E) 17 and then randomized these rats to 9 different groups receiving 3 different means of anesthesia (oxygen/control, propofol, isoflurane) for 3 exposure durations (20, 50, 120 min). Histological analysis of brains from 54 pups revealed that significant number of neurons in anesthetized animals failed to acquire their correct cortical position and remained dispersed within inappropriate cortical layers and/or adjacent white matter. Behavioral testing of 86 littermates pointed to abnormalities that correspond to the aberrations in the brain areas that are specifically developing during the E17. In the second set of experiments, fetal brains exposed to isoflurane at E16 had diminished expression of the reelin and glutamic acid decarboxylase 67, proteins critical for neuronal migration. Together, these results call for cautious use of anesthetics during the neuronal migration period in pregnancy and more comprehensive investigation of neurodevelopmental consequences for the fetus and possible consequences later in life.

Does functional ability in the postoperative period differ between remifentanil- and fentanyl-based anesthesia?

STUDY OBJECTIVES: To compare patients' functional ability in the 24-hour postoperative period following a remifentanil compared to a hypnotic-fentanyl-treated anesthesia regimen using a 24-Hour Functional Ability Questionnaire. DESIGN: Prospective, 1:1 single-blind, randomized, controlled effectiveness study. SETTING: Multicenter study including 156 hospitals and ambulatory surgery facilities. PATIENTS: 2438 patients (1496 outpatients and 942 inpatients) 18 years of age or older, scheduled for elective surgeries under general endotracheal anesthesia, with an expected duration of unconsciousness of > or =30 minutes. INTERVENTIONS: Patients were randomized to receive either intravenous remifentanil (0.5 microg/kg/min for induction and intubation; with the infusion rate decreased to 0.25 microg/kg/min after intubation) or fentanyl (administered according to anesthesiologists' usual practice) as the opioid during surgery. Concomitant hypnotic drugs were propofol and/or isoflurane (with or without nitrous oxide) titrated according to protocol. Transition analgesia with either morphine or fentanyl was given in the remifentanil patients and at the discretion of the anesthesiologists in the fentanyl patients. MEASUREMENTS: A validated set of measurements of functional ability, rather than more traditional clinical psychological methods, to compare the recovery of patients from remifentanil- and fentanyl-treated anesthetic regimens up to 24 hours after surgery. MAIN RESULTS: Remifentanil was statistically superior to fentanyl for the four functional assessments evaluated: walking without dizziness, thinking clearly, concentration, and communicating effectively. These differences reflect events occurring within the first 24 hours after anesthesia and surgery. CONCLUSIONS: A remifentanil-treated anesthetic demonstrated earlier return to some functions than a fentanyl-treated technique. Although functional assessment is a field that is still in its infancy, a questionnaire to assess functional ability during the 24 hours after anesthesia may provide more practical information about anesthetic recovery than previously used, traditional psychomotor evaluations.

Pulmonary thromboembolism during liver transplantation: possible association with antifibrinolytic drugs and novel treatment options.

The authors describe two cases of massive intraoperative pulmonary thromboembolism resulting in cardiovascular collapse during liver transplantation. The potential role of antifibrinolytic drugs is discussed, along with the use of treatment modalities not previously applied in this setting.

Assessing a tool to measure patient functional ability after outpatient surgery.

UNLABELLED: The "24-Hour Functional Ability Questionnaire" (24hFAQ) was developed to measure final recovery and satisfaction 24 h after surgery. We used structured interviews preoperatively to measure baseline patient concerns, and up to 24 h after discharge, to assess patient function and satisfaction. The primary objective was to assess the validity of the newly developed 24hFAQ in the postoperative outpatient setting. The criteria assessed were 1) CONTENT: comparison with expert opinion and patients' views and response frequency distributions for asymptotes and irrelevance, 2) Construct: contribution of cognitive, physical, and satisfaction domains to postoperative functional ability, 3) Discrimination: comparing mean clinical end points with patient satisfaction, and 4) Criterion (predictive) validity: testing that related constructs are best correlated. CONTENT validity was supported by the appropriate frequency distribution of subject responses, by the lack of floor or ceiling effects, and by <2% of responses indicating irrelevance. Construct validity was supported by moderate-to-strong positive interitem correlations within the cognitive and physical domains as predicted a priori. Discriminant validity support was mixed: key symptoms were associated with adverse patient satisfaction, but operating room and postanesthesia care unit residence times were unrelated. Criterion validity was supported by the finding that preoperative concern with key symptoms was independent of postoperative outcomes. The validity assessment presented was the first assessment of the measurement capability of the 24hFAQ in an outpatient postoperative population. These results provide overall support for the validity of the 24hFAQ for use in outpatient populations. IMPLICATIONS: This study assessed the validity of a novel functional ability questionnaire that measured functional status after recovery from anesthesia and satisfaction 24 h after outpatient surgery. The content, construct, discriminant, and criterion (predictive) validities demonstrated the utility of this assessment instrument in the outpatient setting.

Magnesium sulfate potentiates morphine antinociception at the spinal level.

UNLABELLED: Intrathecal magnesium sulfate coinfusion with morphine increases antinociception in normal rats; however, because magnesium also delays the onset of tolerance, it is not clear whether this additional antinociception is a result of potentiated analgesia or tolerance abatement. We examined the antinociceptive interaction of intrathecal (IT) bolus magnesium sulfate and morphine in morphine naive rats and those with mechanical allodynia after a surgical incision. After intrathecal catheter implantation, rats were given preinjections of magnesium or saline, followed by injections of morphine or saline. In morphine naïve rats, IT bolus magnesium sulfate 281 and 375 microg followed by IT morphine 0.25 or 0.5 nmol enhanced peak antinociception and area under the response versus time curve two-to-three-fold in the tail-flick test as compared with morphine alone. Likewise, in rats with incisional pain, IT bolus magnesium sulfate 188 and 375 microg followed by morphine 0.5 nmol reduced mechanical allodynia, whereas morphine 0.5 nmol alone did not. This study suggests that IT magnesium sulfate potentiates morphine at a spinal site of action. IMPLICATIONS: Magnesium sulfate potentiates morphine analgesia when coadministered intrathecally in normal rats, and in an animal model of mechanical allodynia after a surgical incision. These results suggest that intrathecal administration of magnesium sulfate may be a useful adjunct to spinal morphine analgesia.

Aprotinin pretreatment diminishes postischemic myocardial contractile dysfunction in dogs.

UNLABELLED: We evaluated the effect of aprotinin, administered before the onset of acute regional myocardial ischemia, on reversible contractile dysfunction induced by ischemia and reperfusion in pentobarbital-anesthetized dogs. Animals were randomized to receive either aprotinin 30,000 kallikrein inactivator units (KIU)/kg and 7000 KIU x kg(-1) x hr(-1) (n = 8) or equivalent volumes of 0.9% sodium chloride (n = 7) IV 60 min before a 15-min interruption of circumflex coronary artery blood flow and then reperfusion. There were no intra- or intergroup differences in hemodynamic variables or regional myocardial mechanics (sonomicrometry) before onset of ischemia. Immediately before reperfusion, systolic dysfunction characterized by significantly decreased percent systolic shortening was present in the circumflex coronary artery area of both study groups. After reestablishment of perfusion, aprotinin animals had preserved percent systolic shortening whereas saline animals exhibited regional systolic dysfunction. Regional myocardial contractility as assessed by the slope Mw of the preload recruitable stroke work relation was preserved during reperfusion in animals who received aprotinin but depressed in the control group. We conclude that functional recovery from myocardial ischemia-reperfusion injury at normothermia is improved by IV administration of aprotinin before the onset of acute regional myocardial ischemia in physiologically intact dogs. IMPLICATIONS: Administration of clinically relevant doses of aprotinin IV before the onset of regional myocardial ischemia, in contrast to control conditions, preserved regional systolic function and contractility at baseline values after reestablishment of myocardial perfusion in dogs.

The impact of renal dysfunction on aprotinin pharmacokinetics during cardiopulmonary bypass.

UNLABELLED: Aprotinin is a serine protease inhibitor that undergoes metabolism in the kidney. Because elimination is almost entirely renal, the clearance of aprotinin may be reduced in patients with renal insufficiency. Unfortunately, there are no data regarding aprotinin pharmacokinetics in cardiac surgical patients with renal insufficiency or end-stage renal disease (ESRD) undergoing cardiopulmonary bypass (CPB). We, therefore, determined the clearance (ApCl) and elimination half-life (T1/2) of aprotinin in 26 cardiac surgical patients with normal and abnormal renal function (creatinine clearance [CrCl] 0-122 mL/min) undergoing CPB. Subjects were given a 2 million kallikrein inhibiting unit (KIU) initial dose of aprotinin, followed by a 0.25 million KIU/h infusion. No aprotinin was added to the pump prime. Plasma aprotinin concentrations were sampled at 30 min after completion of the loading dose, 30 and 60 min after the onset of CPB, at the end of CPB, and at 8, 24, and 32 h after completion of the loading dose. ApCl was directly related and the elimination T1/2 inversely related to CrCl (r = 0.75 and 0.42, respectively). In patients with a CrCl >50 mL/min, the T1/2 and ApCl were 7.8 h and 53 mL/min, respectively, compared with 19.9 h and 25 mL/min (P < 0.05, P < 0.002, respectively) for patients with ESRD. In conclusion, ApCl is reduced, and T1/2 is prolonged in patients with renal insufficiency or ESRD undergoing CPB. Dosing modifications may be necessary for patients with abnormal renal function undergoing cardiac surgery. IMPLICATIONS: Because aprotinin is metabolized and eliminated in the kidney, its clearance may be reduced in patients with renal insufficiency. Our data suggest that aprotinin clearance is reduced, and aprotinin half-lives are prolonged in patients with renal insufficiency undergoing CPB. Dosing modification may therefore be indicated when aprotinin is administered to these patients for cardiac surgery.

Intrathecal bupivacaine reduces pruritus and prolongs duration of fentanyl analgesia during labor: a prospective, randomized controlled trial.

UNLABELLED: Pruritus is a frequent complication (40%-100%) of intrathecal (IT) fentanyl 25 microg (F) for labor analgesia. The addition of IT bupivacaine 2.5 mg (B) to F has been reported in a nonrandomized series to have a 17.3% incidence of pruritus. This study prospectively evaluated the incidence and distribution of pruritus in laboring parturients receiving IT F + B. Sixty-five laboring parturients were randomly assigned to receive IT F, B, or F + B as part of a combined spinal-epidural technique. Visual analog scores, sensory level, motor strength, and pruritus were recorded before injection and at intervals thereafter. When present, the distribution of pruritus was evaluated. The duration of analgesia was determined as the time from IT drug administration until the patient requested supplemental analgesia. The median duration of analgesia in the F, B, and F + B groups was 62.5, 55.0, and 94.5 min, respectively. Compared with F alone, the combination of F + B led to a decreased frequency of pruritus (36.4% vs 95%). The incidence of facial pruritus (25%) was same in the F + B and F groups; however, the occurrence of pruritus distributed over the rest of the body was significantly more frequent in the F compared with the F + B group. The combination of F + B prolongs the duration of labor analgesia compared with IT F or B alone. F + B also leads to a decreased incidence of pruritus, except in the facial region. IMPLICATIONS: When administered intrathecally with fentanyl 25 microg in laboring parturients, bupivacaine 2.5 mg attenuates the frequency of pruritus on all parts of the body except the face. This combination also results in a rapid onset and prolonged duration of labor analgesia compared with either drug alone.

Antinociceptive potentiation and attenuation of tolerance by intrathecal co-infusion of magnesium sulfate and morphine in rats.

UNLABELLED: N-methyl-D-aspartate (NMDA) antagonists, such as MK801, delay the development of morphine tolerance. Magnesium, a noncompetitive NMDA antagonist, reduces postoperative morphine requirements. The present study was designed to evaluate the effects of intrathecal co-administration of magnesium sulfate with morphine on antinociceptive potentiation, tolerance, and naloxone-induced withdrawal signs. Magnesium sulfate (40-60 microg/h) co-administration for 7 days, similar to MK801 (10 nmol/h), prevented the decline in antinociceptive response compared with morphine (20 nmol/h). Magnesium sulfate (60 microg/h) produced no antinociception, but co-infused with morphine (1 nmol/h), it resulted in potentiated antinociception compared with morphine throughout the 7-day period. Probe morphine doses after 7-day infusions demonstrated a significantly greater 50% effective dose value for morphine 1 nmol/h (109.7 nmol) compared with saline (10.9 nmol), magnesium sulfate 60 microg/h (10.9 nmol), and magnesium sulfate 60 microg/h plus morphine 1 nmol/h (11.2 nmol), which indicates that magnesium had delayed morphine tolerance. Morphine withdrawal signs after naloxone administration were not altered by the co-infusion of magnesium sulfate. Cerebrospinal fluid magnesium levels after intrathecal magnesium sulfate (60 microg/h) for 2 days increased from 17.0 +/- 1.0 microg/mL to 41.4 +/- 23.6 microg/mL, although serum levels were unchanged. This study demonstrates antinociceptive potentiation and delay in the development of morphine tolerance by the intrathecal coinfusion of magnesium sulfate and morphine in the rat. IMPLICATIONS: The addition of magnesium sulfate, an N-methyl-D-aspartate antagonist, to morphine in an intrathecal infusion provided better analgesia than morphine alone in normal rats. These results suggest that intrathecal administration of magnesium sulfate may be a useful adjunct to spinal morphine analgesia.

An in vivo evaluation of four spinal needles used for the combined spinal-epidural technique.

UNLABELLED: The purpose of this study was to evaluate four pencil-point spinal needles commonly used for combined spinal-epidural (CSE) anesthesia. Four hundred-seven consecutive parturients undergoing cesarean delivery or labor analgesia received a CSE block with a randomly selected pencil-point spinal needle (Becton-Dickinson [B-D] 27-gauge, 119-mm Whitacre; B-D 27-gauge, 120-mm Durasafe; B-D 25-gauge, 120-mm Durasafe; or International Medical Devices' 26-gauge, 124-mm Gertie Marx). Success in obtaining cerebrospinal fluid (CSF) and the incidence of transient paresthesias and postdural puncture headache (PDPH) were compared by using chi2 testing; P < 0.05 was considered significant. Failure to obtain CSF (3%-5%) was not significantly different among spinal needles. The Gertie Marx 26-gauge needle was associated with significantly more paresthesias (29%) than the Whitacre 27-gauge needle (17%). The combined incidence of paresthesias with the Durasafe 25-gauge and Gertie Marx 26-gauge spinal needles (28%) was greater than the combined incidence of paresthesias with the Durasafe 27-gauge and Whitacre 27-gauge needles (18%). The incidence of PDPH did not differ among the four pencil-point spinal needles. We conclude that longer spinal needles are associated with a significantly more frequent incidence of transient paresthesias without residual effects. IMPLICATIONS: The use of four pencil-point spinal needles in the combined spinal-epidural technique is associated with an inconsequential incidence of spinal headache, a low incidence of paresthesias that are transient with no long-term effects, and a high degree of success independent of spinal needle length.

Peripheral vascular surgery: does anesthetic management affect outcome?

Several recent articles have examined the effect of anesthetic technique on outcome in patients undergoing peripheral vascular surgery. This review examines the recent literature and evaluates the role of new data in advancing current understanding of the impact of anesthetic management on outcome in this high-risk population.