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Biomedical subjects

N L Herman

Publications and source records attributed to N L Herman.

14 recordsLinked to original sources
PubMed2000

Transfer of methohexital across the perfused human placenta.

STUDY OBJECTIVES: To evaluate the transfer properties of methohexital and the influence of protein binding using the in vitro human placental perfusion model. DESIGN: Fresh term human placentae from healthy parturients were perfused bidirectionally via a cannulated fetal chorionic artery and vein and needles placed into the maternal intervillous space. Maternal-to-fetal (M-->F) and fetal-to-maternal (F-->M) transfer and ultimate distribution of methohexital was investigated using a closed (recirculating) placental perfusion model. SETTING: Obstetric anesthesia laboratories of two university medical centers. PATIENTS: No patient participation occurred as placentae were obtained after delivery. INTERVENTION: M-->F and F-->M transfer of methohexital was compared in vitro in perfusates with equal protein concentrations (2 g/100 mL in both perfusates) or albumin-simulated physiologic protein binding concentrations (maternal 8 g/100 mL; fetal 4 g/100 mL). MEASUREMENTS AND MAIN RESULTS: Data obtained consisted of measurements of methohexital and antipyrine concentrations by high-performance liquid chromatography. Glucose and lactate concentrations and perfusate loss were measured to assess placental viability. Methohexital protein binding was assessed at 2, 4, and 8 g/100 mL of albumin by equilibrium dialysis. The transfer index of 0.83 +/- 0.11 for the M-->F perfusions was significantly greater (p < or = 0.05) than in the F-->M direction (0.61 +/- 0.04) when albumin concentration was equal in both perfusates. This transfer asymmetry disappeared when albumin concentrations simulating maternal (8 g/100 mL) versus fetal (4 g/100 mL) protein concentrations in the perfusate were used (M-->F 0.87 +/- 0.12 and F-->M 0.95 +/- 0.11). CONCLUSION: Methohexital readily crosses the placenta in both directions. Protein binding has significant effects on the degree of transfer of methohexital at any time when compared with antipyrine and its ultimate fetal/maternal distribution.

Adolescent↗
PubMed1999

Analgesia, pruritus, and ventilation exhibit a dose-response relationship in parturients receiving intrathecal fentanyl during labor.

UNLABELLED: Several studies have characterized the 50% and 95% effective doses (ED50 and ED95, respectively) of intrathecal sufentanil for labor analgesia. Few have investigated these same criteria for the less expensive alternative, fentanyl. In addition, the ventilatory effects of intrathecal fentanyl at clinically relevant doses are unclear. We performed this study to establish the dose-response relationship of intrathecal fentanyl for both analgesia and ventilatory depression. Ninety parturients in active early labor (< or = 5 cm dilation) received intrathecal fentanyl 5, 7.5, 10, 15, 20, or 25 micrograms in a double-blinded, randomized fashion (n = 15 patients in each group). Parturients were monitored for degree of pain (measured using a 100-mm visual analog pain scale), blood pressure, arterial oxygen saturation (SaO2), respiratory rate, ETCO2, and fetal heart rate 0, 1, 5, 10, 15, 20, 25, and 30 min after the administration of intrathecal fentanyl. An absolute visual analog pain scale score < or = 25 mm was defined a priori as analgesic success. The percentage of parturients who achieved analgesic success was used to construct quantal dose-response curves, from which the ED50 and ED95 values were derived for the total population (mixed parity) and the nulliparous and multiparous subpopulations separately. Overall ED50 and ED95 values (95% CI) were 5.5 (3.4-7.2) and 17.4 (13.8-27.1) micrograms, respectively. Nulliparous values were lower (5.3 and 15.9 micrograms, respectively) than multiparous values (6.9 and 26.0 micrograms, respectively) but were within the 95% CIs of the total population. Pruritus incidence in parturients with analgesic success displayed a dose-response relationship identical to that seen for analgesia. ETCO2 displayed a dose-related increase, particularly at doses > or = 15 micrograms, without concomitant changes in respiratory rate or SaO2, which suggests a decrease in tidal volume. Even in the absence of overt signs or symptoms of somnolence, intrathecal fentanyl at doses within the effective analgesic range induced a change in ventilation that may last longer than the 30-min period we studied. IMPLICATIONS: Intrathecal fentanyl induces rapid and satisfying dose-dependent analgesia in early labor; however, it also produces dose-related decreases in ventilation in the absence of overt somnolence.

Adult↗
PubMed1998

Determination of the analgesic dose-response relationship for epidural fentanyl and sufentanil with bupivacaine 0.125% in laboring patients.

STUDY OBJECTIVE: To establish the analgesic effective doses as defined as a visual analog pain scale (VAS) of at least 10 for 95% of parturients (ED95) receiving either epidural fentanyl or sufentanil with bupivacaine 0.125% for labor analgesia. DESIGN: Double-blind, randomized controlled study. SETTING: Two tertiary-care teaching hospitals. PATIENTS: 100 female patients, at full-term pregnancy, in active early labor (< 5 cm cervical dilation) and requesting obstetric anesthesia services for labor analgesia. INTERVENTIONS: Patients were randomized and equally distributed to receive one of ten epidural dosing regimens of bupivacaine 0.125% alone or with either fentanyl 25, 50, 75, or 100 micrograms or sufentanil 5, 10, 15, 20, or 25 micrograms in a 10-ml bolus after a 3-ml test dose of bupivacaine 0.25%. MEASUREMENTS AND MAIN RESULTS: VAS scores were obtained from each parturient using a 10-cm plastic VAS slide rule at times 0, 1, 5, 10, 15, 20, 25, and 30 minutes, and then again when the patient requested additional analgesia. Analgesic duration and demographic and obstetric data also were obtained. Using a log-probit dose-response analysis, analgesic success as defined as a VAS of at least 10 with each opioid dose was plotted and an ED95 value of 8 micrograms and 50 micrograms was established for sufentanil and fentanyl, respectively, in bupivacaine 0.125%. No statistical difference was detected for analgesic duration or incidence of side effects between analgesic groups. CONCLUSIONS: Epidural analgesia with fentanyl and sufentanil in bupivacaine 0.125% behaves in a dose-response fashion allowing for the determination of equipotent dose of each.

Adult↗
PubMed1997

A comparison of catheter vs needle injection of local anesthetic for induction of epidural anesthesia for cesarean section.

It is generally believed that bolus injections of local anesthetic through an epidural needle produce a more rapid onset of blockade, but at the expense of an increased incidence and severity of hypotension, whereas intermittent injections through a catheter take longer to achieve adequate anesthesia but with a lower risk of hypotension. The present study investigated two commonly used needle and catheter epidural injection techniques for differences in speed of onset of surgical anesthesia and incidence and severity of hypotension. Term parturients scheduled for elective cesarean section were randomized into two groups to receive epidural anesthesia with intermittent injection either through the epidural needle (n = 44) or via a previously placed catheter (n = 44). The incidence and severity of hypotension was similar in the two groups. No significant difference was found for the time to onset of surgical anesthesia. In the absence of benefits of needle injection, incremental catheter administration of local anesthetic with its multiple safety advantages is the technique of choice for induction of epidural anesthesia for cesarean section.

Clinical Trial↗
PubMed1997

The pharmacokinetics of epidural lidocaine and bupivacaine during cesarean section.

We studied the maternal pharmacokinetics of epidural lidocaine and bupivacaine in 20 healthy parturients with institutional review board approval and written, informed consent. Epidural anesthesia was induced using either 2% lidocaine with epinephrine 1:200,000, n = 10, or 0.5% plain bupivacaine, n = 10. Maternal arterial (Ma) blood was sampled at regular intervals and umbilical venous (Uv) blood at delivery. Results for lidocaine and bupivacaine, respectively, were (mean +/- SEM): age 30.4 +/- 1.5 and 24.7 +/- 1.6 yr; weight 74.0 +/- 4.2 and 74.9 +/- 4.5 kg; duration of surgery 55.5 +/- 4.3 and 53.1 +/- 3.5 min; epidural dosage 6.1 +/- 0.6 and 1.5 +/- 0.2 mg/kg; elimination half-life 113.9 +/- 5.6 and 110.4 +/- 20.4 min; plasma clearance 6.1 +/- 0.4 and 13.6 +/- 1.3 mL.kg-1.min-1; volume of distribution 0.98 +/- 0.1 and 1.67 +/- 0.3 L/kg; time to peak concentration 31 +/- 2.3 and 40.5 +/- 1.7 min; peak Ma concentration 6.4 +/- 0.65 and 0.8 +/- 0.1 microgram/mL; and Uv/Ma gradient 0.43 +/- 0.05 and 0.26 +/- 0.1. Peak Ma lidocaine concentrations in 2 of 10 patients reached potentially toxic levels without producing clinical toxicity, whereas peak bupivacaine Ma concentrations never approached levels considered unsafe. The results suggest that epidural bupivacaine reliably produces acceptable Ma concentrations below the toxic range.

Adolescent↗
PubMed1997

Determination of the dose-response relationship for intrathecal sufentanil in laboring patients.

Multiple studies have investigated the efficacy of intrathecal opioids, particularly sufentanil, in laboring parturients. However, until the important pharmacological indices of the 50% and 95% effective doses (ED50 and ED95, respectively) are defined, reliable comparative studies among drugs at equipotent doses cannot be performed. This study was performed to establish the dose-response relationship of intrathecal sufentanil analgesia in labor. Sixty parturients presenting in active labor received intrathecal sufentanil 2.5 (n = 10), 5.0 (n = 10), 7.5 (n = 10), 10.0 (n = 10), 12.5 (n = 10), or 15.0 (n = 10) microg in a blind, randomized fashion. Patient 100-mm visual analog pain scale (VAS) scores, fetal heart rate (FHR), blood pressure, and heart rate were recorded at 0, 1, 5, 10, 15, 20, 25, and 30 min after administration of sufentanil and then again when the patient requested additional analgesia. Absolute VAS < or =25 mm was considered an analgesic success. Percent responders was used to construct a dose-response curve and calculate ED50 and ED95. The ED50 and ED95 for intrathecal sufentanil in laboring parturients were 2.6 (1.8-3.2, 95% confidence interval) and 8.9 (7.5-11.5) microg, respectively. There was a trend toward increasing analgesic duration with increasing sufentanil dose. The maternal side effect profile was not different among groups. FHR did not appreciably change for any group or individual studied. Assisted delivery and cesarean section rates were similar for all groups. Intrathecal sufentanil provides rapid onset of analgesia for labor. The ED50 and ED95 values established in this study should help to provide benchmarks both for the safe clinical use of intrathecal sufentanil for labor and for future comparison studies with other intrathecal analgesic techniques.

Adult↗
PubMed1996

Cricoid pressure: teaching the recommended level.

The Sellick maneuver or cricoid pressure is an effective means of preventing passive aspiration of gastric contents. Recent studies recommend a pressure of 20 newtons (N) when the patient is awake, increasing to 30-40 N with unconsciousness. This study was proposed to determine whether with education and practice, anesthesia providers and assistants could be taught a recommended cricoid pressure and retain this skill. Cricoid force was measured using a life-size laryngotracheal model on a calibrated infant scale. Fifty-three participants were divided into six groups: MD faculty; CA-1, 2, and 3 Residents; certified registered nurse anesthetists (CRNA); and Others. Each was asked to apply pressure to the blinded model to simulate application of the Sellick's maneuver to an "awake" and "unconscious" patient on four occasions: before instruction of the recommended pressures (Preinstruction), after being informed of the recommended magnitudes of 20 N/awake and 30-40 N/anesthetized (Postinstruction), after a period of unblinded practice (Postpractice), and 3 mo or longer after practice (Follow-up). Initial attempts revealed inadequate force by all participants, "awake" and "anesthetized". All participants were able to learn the recommended amount of applied pressure and were able to retain this knowledge after 3 mo. This model represents an easy and practical means of teaching the application of the optimal level of force to practitioners and assistants.

Analysis of Variance↗
PubMed1996

Effects of fetal pH on local anesthetic transfer across the human placenta.

BACKGROUND: Fetal acidemia increases umbilical venous bupivacaine concentrations in the in situ rabbit model. The authors studied the effects of decreasing fetal pH on the rate of maternal to fetal (M-->F) clearances of lidocaine, bupivacaine, 2-chloroprocaine, and antipyrine (a nonionic marker of placental transfer) across the isolated, dual perfused, human placental cotyledon. METHODS: Maternal to fetal clearances of bupivacaine, lidocaine, 2-chloroprocaine, and antipyrine were determined at fetal pH (7.4), during progressive fetal acidemia (pH 7.2-->7.0-->6.8), and after recovery to fetal pH 7.4 in experiments with both low protein state and in those with in vivo maternal and fetal protein-binding potentials. RESULTS: Placental transfer of all three agents increased linearly as the fetal pH decreased. Antipyrine transfer was unaffected. Clearance of lidocaine and bupivacaine, but not 2-chloroprocaine, returned to baseline when fetal pH was restored to 7.4. When maternal and fetal protein-binding potentials were increased, clearance at fetal pH 7.4 of bupivacaine, but not lidocaine, decreased significantly. During fetal acidemia, the transfer of both agents increased, but to a lesser extent than in the low protein concentration experiments. CONCLUSIONS: Increasing the pH difference between maternal and fetal perfusates promotes M-->F passage of unionized lidocaine, bupivacaine, and 2-chloroprocaine. This likely results from an increased proportion of ionized local anesthetic in the acidemic fetal perfusate and consequent widening of the M-->F concentration gradient of the unionized form. Transfer of lidocaine and bupivacaine was limited by the maternal protein binding.

Anesthetics, Local↗
PubMed1986

Alterations in cardiac [14C]deoxyglucose uptake induced by two renal afferent stimuli.

The reflex effects of renal afferents on the heart were studied in pentobarbital-anesthetized rats (400-425 g) using 2-[14C]deoxyglucose (DG). Three groups of rats were given a single bolus injection of DG (100 mu Ci/kg) 1) six controls, 2) four with periodic electrical stimulation of the proximal end of a cut renal nerve (2 Hz, 0.5-ms width) and 1-mA current, and 3) six with intermittent renal venous occlusion (unilateral). Forty-five minutes after injection the heart was removed, cooled quickly, and frozen-sectioned. Sections 20 micron thick were exposed to film for 12 days. The resulting autoradiographs were scanned using a computerized densitometer, and these densities were converted to relative glucose utilization (GlU, mumol X 100 g-1 X min-1) using the lumped constant for rat brain. Both renal venous occlusion and renal afferent nerve stimulation resulted in a decrease in blood pressure of 6.7 +/- 0.6 mmHg (P less than 0.001) and 7.3 +/- 0.7 mmHg (P less than 0.001) and heart rate-blood pressure product of 5.6 +/- 0.7% (P less than 0.001) and 8.8 +/- 0.8% (P less than 0.001), respectively, and afferent renal nerve stimulation induced a decrease in heart rate of 7.2 +/- 0.9 beats/min (P less than 0.01). However, when compared with control, renal venous occlusion induced a significant increase in GlU in left ventricular myocardium (LV myo, P less than 0.05), endocardium (LV endo, P less than 0.001), and papillary muscle (LV pap, P less than 0.001), whereas afferent renal nerve stimulation induced a significant increase in GlU in LV endo (P less than 0.05) and LV pap (P less than 0.002) only. This study shows both a reflex increase in GlU for the rat heart and a decrease in heart rate with either renal vein occlusion or afferent renal nerve stimulation.

Afferent Pathways↗
PubMed1986

Ventilation of a rat with a large-animal respirator.

Rats were effectively ventilated with 100% O2 mixed with room air utilizing a modified tracheostomy tube and a Bird Mark 7 respirator to maintain arterial blood gases within normal limits. A 3-cm segment of rubber pilot tubing was attached to a 15-mm respiratory connector and a 3-cm piece of polyethylene catheter tubing was fitted snugly into the other end. The catheter was inserted and secured into the trachea of 250- to 500-g Sprague-Dawley rats with the adaptor hose of the respirator fitted onto the 15-mm connector following tracheostomy. Manometer and inspiratory flow rate controls of the respirator were set to their minimum operating position. Appropriate rate control adjustments were made when necessary as determined by arterial blood gas measurements. By use of the above ventilation system, adequate arterial blood gases of anesthesized rats can be maintained for greater than 3 h.

Animals↗
PubMed1982

Splenic afferents and some of their reflex responses.

Afferent nerve activity was recorded from the distal ends of cut splenic nerves in pentobarbital- (35 mg/kg) anesthetized mongrel dogs (15-20 kg). Increases in splenic venous pressure (SVP) produced either by manual compression of discrete portions of the spleen or splenic contraction produced by injection of epinephrine (100 micrograms) into the splenic artery or vein of an occluded spleen produced significant increases in SVP and splenic afferent nerve activity. Increases in splenic afferent nerve activity were linearly related to increases in SVP. Histological sections of nerves from which afferent recordings were obtained demonstrated that all afferents were unmyelinated C-fibers. Electrical stimulation of the cut central end of splenic nerves resulted in marked reflex increases in both renal and cardiopulmonary sympathetic efferent nerve activity that remained elevated throughout the stimulation period. Reflex increase in cardiopulmonary sympathetic efferent nerve activity was associated with increases in right (22-45%) and left (11-19%) ventricular contractile force measured with Brodie-Walton strain gauge transducers, in heart rate (5-15 beats/min), and in blood pressure (5-10 mmHg). This study is the first to demonstrate both the existence of low-pressure baroreceptors in the spleen and that these splenic afferents can reflexly alter cardiopulmonary and renal sympathetic efferent nerve activity, heart rate, ventricular contractile force, and systemic blood pressure.

Afferent Pathways↗