Blocks of limited haplotype diversity revealed by high-resolution scanning of human chromosome 21.

Global patterns of human DNA sequence variation (haplotypes) defined by common single nucleotide polymorphisms (SNPs) have important implications for identifying disease associations and human traits. We have used high-density oligonucleotide arrays, in combination with somatic cell genetics, to identify a large fraction of all common human chromosome 21 SNPs and to directly observe the haplotype structure defined by these SNPs. This structure reveals blocks of limited haplotype diversity in which more than 80% of a global human sample can typically be characterized by only three common haplotypes.

Labour analgesia. A risk-benefit analysis.

The pain associated with labour can be severe. The ideal labour analgesic does not exist and systemic opioids provide little relief. Nausea, vomiting and sedation are common adverse effects of systemic opioids. Paracervical block can relieve only the pain of the first stage of labour. The duration of analgesia obtained using paracervical block is limited and repeat blocks increase the risk of direct fetal injection. Epidural analgesia effectively relieves labour pain. The insertion of an epidural catheter can provide continuous analgesia throughout labour. In addition, the catheter can be used to provide surgical anaesthesia, should operative delivery be required. Epidural local anaesthetics commonly produce maternal hypotension and motor blockade. However, opioids potentiate the effect of epidural local anaesthetics. Thus, concomitant epidural opioid injection allows the use of lower concentrations of local anaesthetics, decreasing the frequency and severity of hypotension and motor blockade. Epidural analgesia has other, potentially catastrophic, adverse effects but, with safe clinical practice, these problems are extremely rare. Intrathecal injection of opioids or local anaesthetics also effective labour analgesia. However, no single intrathecal drug or drug combination reliably provides analgesia for the duration of labour. Many clinicians use both intrathecal and epidural analgesia as a combined spinal-epidural technique. This approach provides the rapid onset of intrathecal drugs and the flexibility of continuous epidural block. Fetal heart rate decelerations occasionally follow the use of any of the above labour analgesic techniques. Most studies of the aetiology of fetal heart rate decelerations have focused on factors unique to each analgesic technique. However, the similar timing and appearance of fetal bradycardia suggests a common cause. Induction of maternal analgesia may transiently alter the balance between factors encouraging and inhibiting uterine contraction. A temporary increase in the uterotonic effects of endogenous or exogenous oxytocin may then produce a tetanic uterine contraction with subsequent decrease fetal oxygen delivery and resultant fetal bradycardia. Regardless of aetiology, these bradycardias are transient and should not produce maternal or fetal morbidity. Much controversy surrounds the effects of analgesia, especially epidural block, on the course and outcome of labour. Various studies have reported that epidural analgesia slows labour, increases the incidence of malposition of the fetal head, increases the need for forceps delivery and increases the risk of caesarean delivery. Most of the studies reporting these effects are retrospective and nonrandomised. More careful studies suggest that specific anaesthetic techniques (i.e. local anaesthetic-opioid mixtures) or obstetrical management can limit or eliminate these 'risks' of epidural labour analgesia.

Intrathecal sufentanil (5 vs. 10 microg) for labor analgesia: efficacy and side effects.

BACKGROUND AND OBJECTIVES: Despite growing popularity, there are few studies examining the relative efficacy of different doses of intrathecal sufentanil for labor analgesia. This prospective, randomized, double-blind study compared the efficacy and side effects of 5 and 10 microg intrathecal sufentanil. METHODS: Sixty-three healthy, laboring, term parturients < or =5 cm cervical dilation participated in this study. In a randomized, double-blind fashion, patients received 5 or 10 microg intrathecal sufentanil as part of a combined spinal epidural technique. Patients rated pain, itching, nausea, and sedation on verbal analog scales before and every 10 minutes after drug injection. We also recorded maternal blood pressure and peripheral oxygen saturation before and every 10 minutes after drug injection. Before and 30 and 60 minutes after drug injection, we measured maternal end-tidal CO2. RESULTS: Both doses of sufentanil provided adequate analgesia. Although 10 microg sufentanil produced slightly more profound analgesia, the duration of pain relief did not differ between the two groups. Both drug doses were associated with significant increases in itching and end-tidal CO2. The 10-microg dose was associated with more sedation and a greater decrease in SaO2. CONCLUSIONS: Both 5 and 10 microg intrathecal sufentanil provided adequate labor analgesia. Both doses were associated with measurable spinal (itching) and supraspinal (sedation, respiratory depression) side effects.

Are combined spinal-epidural catheters reliable?

The combined spinal-epidural (CSE) technique can rapidly relieve labor pain. However, the location of the epidural catheter is initially uncertain. In an emergency, this untested catheter may fail to provide adequate anesthesia. This study compared the efficacy of catheters placed as a part of an epidural or needle-though-needle CSE technique in laboring women. Patients requesting pain relief received either epidural (n=601) or CSE (n=1061) analgesia. All patients had a 20 gauge, closed tip multi-holed polyamide catheter. (B. Braun Medical, Inc.) inserted 2-8 cm into the epidural space. Catheters were tested to rule out intrathecal and intravascular location. Then, epidural patients received 10-20 ml local anesthetic +/- opioid in divided doses. CSE patients received and infusion of 0.083% bupivacaine with opioid at 10-15 ml/h. Of the 1495 catheters that were adequately tested, those inserted as part of a CSE technique were more likely to produce bilateral sensory change and adequate analgesia than were those inserted without prior spinal analgesia (98.6% vs 98.2%, P<0.02). Stand-alone epidural catheters were more likely to produce neither sensory change nor analgesia than those inserted as part of CSE technique (1.3% vs 0.2%, P<0.02). The only catheters that failed completely and were not intravascular were stand-alone epidural catheters. In this clinical setting, catheters inserted as part of a CSE technique had a high probability of being in the epidural space and functioning appropriately.

Histamine release following intrathecal administration of morphine for cesarean section.

We present a case of unusually profound, prolonged hypotension after induction of spinal anesthesia for cesarean section. The patient, a healthy parturient at 26 weeks gestation, received 0.75% bupivacaine, 15 mg and morphine, 0.15 mg by subarachnoid injection. Systolic blood pressure rapidly fell to below 80 mmHg despite left uterine displacement, 10 l of balanced saline solution, ephedrine 210 mg and phenylephrine 1000 microg. At the end of the operation we noted a pruritic, erythematous, circumscribed, raised rash, consistent with urticaria, over the patient's trunk, legs, arms and face. This rash persisted for 2 days. We postulate that the excessive hypotension following spinal anesthesia in this parturient was the result of intrathecal morphine induced histamine release.

Advance prediction of hypotension at cesarean delivery under spinal anesthesia.

Cardiovascular responses to supine inferior vena cava compression might predict hypotension risk during elective cesarean delivery using spinal anesthesia. In this pilot study we investigated 27 women before operation by taking blood pressure and heart rate measurements for 5 min in the left lateral position, 5 min supine, and then performed one further reading in the left lateral position and one sitting. Anesthesia with hyperbaric bupivacaine was rigorously standardised. A pre-operative 'supine stress test', combining an increase in maternal heart rate of greater than 10 beats/min or leg flexion movements while supine, was analysed. A positive supine stress test (SST) was 4.1 times more frequent in those with severe systolic hypotension below 70% of baseline (12 out of 16 women) than in those without (2 out of 11 women), with a sensitivity of 75% (95% C.I. 48% to 93%) and specificity of 82% (95% C.I. 48% to 98%). A positive test was associated with twice as much vasopressor use as a negative test (30.7 +/-/14.5 mg versus 13.5 +/-/ 9.9 mg; P = 0.0014). Unlike the SST, cardiovascular responses to the change from recumbent to sitting (tilt test) were not useful as a predictor of hypotension.

Anesthesia for reduction of uterine incarceration: report of two cases.

We present two cases in which anesthesia was needed for the reduction of uterine incarceration. The first case was managed with a combined spinal/epidural technique and the second with a single intrathecal injection of opioid and low dose local anesthetic. The anesthetic issues pertinent to the reduction of an incarcerated uterus are discussed and the literature briefly reviewed.

The incidence of herpes simplex virus labialis after cesarean delivery.

Epidural and subarachnoid opioids have been associated with the development of oral herpes simplex lesions. Because of this risk, some anesthesiologists avoid neuraxial morphine in parturients with a history of herpes simplex virus labialis. When we began using neuraxial opioids for analgesia after cesarean delivery, we did not see any increased incidence of facial lesions. To confirm this impression, we studied 357 consecutive parturients presenting for elective or emergent cesarean delivery between 1 December 1989 and 27 June 1990. The women received spinal, epidural, or general anesthesia. Two hundred and one women received either spinal or epidural morphine, the remaining 156 parturients received only systemic opioids for postoperative analgesia. An investigator saw each patient daily until discharge. Only 11 patients (3%) developed oral lesions while hospitalized. None of these women had severe lesions. Neuraxial morphine did not increase the risk of labial lesions significantly (3.5% vs. 2.6%). Despite published data to the contrary, we found no correlation between neuraxial morphine and the risk of facial herpes virus lesions in women after cesarean delivery. We offer patients the option of neuraxial morphine for analgesia after cesarean delivery despite any history of oral herpes lesions.

Intrathecal meperidine for labor analgesia: preliminary communication.

The authors administered intrathecal meperidine 10 mg to 10 healthy laboring women to determine its analgesic quality, onset, duration, and side-effect profile. When patients requested pain relief, we injected 10 mg preservative-free meperidine in 1 ml normal saline through a 32 gauge spinal catheter. We administered a second dose of meperidine 10 mg if analgesia was inadequate at 10 min. Additional doses of intrathecal meperidine or bupivacaine were administered on request. All patients received local anesthetic intrathecally or by infiltration for delivery. Eight patients were pain-free following meperidine 10 mg, the other 2 patients were comfortable after the second 10 mg meperidine dose. Three patients did not request further labor analgesics and delivered 58, 66 and 244 min following their initial injection of intrathecal meperidine. The mean duration of analgesia in the other 7 patients was 136 +/- 58 (mean +/-SD) min. Six of the 10 women in the study delivered vaginally; 3 spontaneously and 3 with vacuum or forceps assistance. Four patients delivered by cesarean section for failure to progress. Side-effects (which were easily treated) consisted of: pruritus (n = 1), vomiting (n = 2), hypotension (n = 2) and changes in fetal heart rate pattern (n = 5). All infants were vigorous and had good Apgar scores at birth. In conclusion, intrathecal meperidine is a promising labor analgesic, but the effect of meperidine on maternal blood pressure, fetal heart rate pattern, and the progress of labor need to be determined.

Efficacy and financial benefit of an anesthesiologist-directed university preadmission evaluation center.

STUDY OBJECTIVE: To study the effectiveness of an anesthesiologist-directed preadmission evaluation center (PEC) in our institution. DESIGN: I: Preoperative test costs were measured on two sets of patients undergoing same-day surgery. II: Rate of cancellation was measured on all patients undergoing same-day surgery in a subsequent one-year time period. SETTING: The PEC, short procedure unit, and same-day admission unit of a university hospital. PATIENTS: I: 3,062 male and female patients undergoing same-day surgery between January 1, 1992, and August 31, 1992. II: 9,454 male and female patients undergoing same-day surgery between July 1, 1993, and June 30, 1994. INTERVENTIONS: Age, ASA physical status, type of surgery performed, and tests ordered were recorded in two groups of same-day surgical patients. Group S had testing primarily ordered by surgeons, augmented by the anesthesiologists in the PEC. Group A had testing primarily ordered by the anesthesiologists in the PEC, but surgeons could still order tests they felt necessary. On the day of surgery, the attending anesthesiologist recorded any additional testing that was required or would have altered intraoperative management. In a follow-up study, cancellations of same-day surgical patients were recorded for a one-year period. MEASUREMENTS AND MAIN RESULTS: I: With the exception of complete blood counts with differentials, significantly fewer tests were ordered in Group A than Group S. These changes produced an average cost savings of $20.89 per patient. There were no recorded cancellations or apparent alterations in intraoperative management attributable to inadequate testing. II: Of the 9,454 same-day procedures from 7/1/93 to 6/31/94, 66 were cancelled on the day of the procedure. None of the patients seen in the PEC were cancelled due to causes possibly preventable by a PEC, unlike the cases of 4 patients who had not been evaluated in teh PEC and were cancelled. CONCLUSION: A PEC, in which the anesthesiologist primarily orders preoperative tests and approves patients' readiness for surgery, is both an efficient and cost-effective system.

Patient variables and the subarachnoid spread of hyperbaric bupivacaine in the term parturient.

To determine if age, height, weight, body mass index, or vertebral column length significantly influence the distribution of sensory analgesia or anesthesia after subarachnoid injection of hyperbaric bupivacaine, 52 women presenting for cesarean section were studied. All received 15 mg hyperbaric bupivacaine via subarachnoid injection at L-2 or L-3. Fifteen minutes after injection, while the women lay supine on a horizontal operating table, the maximum cephalad extent of sensory analgesia (loss of sensation of sharpness to pin prick) and anesthesia (loss of sensation of light touch) was determined. Age (20-42 yr), height (146.9-174.0 cm), weight (55.5-136.4 kg), body mass index (19.2-50.0 kg/m2), and vertebral column length (49.6-67.0 cm) did not correlate with the spread of sensory blockade. In conclusion, in parturients of age, height, weight, body mass index, and vertebral column length within the aforementioned ranges, it is not necessary to vary the dose of injected hyperbaric bupivacaine with changes in any of the patient variables studied.

Height, weight, and the spread of subarachnoid hyperbaric bupivacaine in the term parturient.

Using a standardized technique, spinal anesthesia was induced in 50 term parturients to study the correlation between patient height, weight, and body mass index (BMI) and the spread of sensory blockade. All patients received 12 mg hyperbaric bupivacaine while in the right lateral decubitus position on a horizontal operating table. Immediately after drug injection, the women were turned to the supine horizontal position with left uterine displacement. Fifteen minutes after drug injection, the level of analgesia to pinprick was measured. Linear regression analysis revealed no significant correlation between height (146-175 cm), weight (57.3-93.6 kg), or body mass index (21-38 kg/m2) and the spread of spinal anesthesia (T7-C8). It is concluded that, in term parturients, patient height, weight, or BMI does not significantly affect the spread of hyperbaric spinal anesthesia.

Spinal opioid analgesia for labor.

Intrathecal opioids and the combined spinal/epidural technique provide new tools for the obstetrical anesthesiologist. With intrathecal opioids, we can rapidly and safely relieve the pain of labor without maternal sedation or motor blockade. Intrathecal sufentanil 10 micrograms provides 1 to 2 hours of excellent analgesia during the first stage of labor. We often use this technique in women who would otherwise obtain marginal pain relief from systemic opioids. Unless morphine is used, the side effects induced by intrathecal opioids are usually mild and easily treated. In our practice, combined spinal/epidural labor analgesia has rapidly gained wide acceptance by patients, nurses, obstetricians, and anesthesiologists. Continuous spinal analgesia, although theoretically appealing, requires further refinement.

Effect of gravity on the spread of extradural anaesthesia for caesarean section.

The effect of gravity on the spread of extradural anaesthesia was evaluated in a series of parturients undergoing elective Caesarean section. Following placement of an extradural catheter, 25 patients were placed 30-40 degrees head-up for 20 min during the administration of the local anaesthetic drug; 25 additional patients remained supine during injection. Extradural anaesthesia was induced with 3% 2-chloroprocaine 23 ml and analgesia to pinprick assessed at 5-min intervals. Additional drug was given after 20 min, if required. There were no differences in the rate of onset of sacral blockade or in the extent of neural blockade between the two groups. The semi-upright position was not necessary to ensure adequate sacral anaesthesia for Caesarean section.

Continuous spinal anesthesia after unintentional dural puncture in parturients.

Headache after unintentional dural puncture with 17- or 18-gauge needles represents a significant source of anesthetic-induced maternal morbidity. We performed this study to determine whether inserting a catheter into the subarachnoid space after dural puncture can significantly alter the incidence of headache. Thirty-five women, requesting labor analgesia, suffered a dural puncture during attempts to identify the epidural space using an 18-gauge Hustead needle (bevel oriented parallel to the longitudinal axis of the back). Subsequently, the anesthesiologist inserted a 20-gauge polyamide catheter into the CSF and provided continuous spinal anesthesia throughout labor and delivery. A second group of 21 women suffered dural puncture with the same epidural technique but without subarachnoid catheter insertion. These women subsequently received lumbar epidural anesthesia. After delivery, we visited all women daily until discharge and questioned them about the presence and severity of headache. Neither the incidence of headache nor the need for therapeutic blood patch differed significantly between the two groups of women. No other anesthetic related complications ensued. Continuous spinal anesthesia after unintentional dural puncture does not decrease the incidence of headache in parturients.

Maternal and fetal effects of isoproterenol in the gravid ewe.

Detection of the intravascular placement of epidural catheters is an important but difficult task. In this study, we evaluated maternal and fetal hemodynamic responses to intravenous (i.v.) and epidural injection of isoproterenol (ISO), a proposed chronotropic test dose, in gravid ewes. Near-term, chronically instrumented, gravid ewes with single fetuses were studied at least 48 h after surgery. We continuously recorded maternal heart rate (MHR), systemic and pulmonary blood pressures, uterine blood flow (UBF), and fetal blood pressure and heart rate. Maternal cardiac output was measured by thermodilution. In random sequence, each ewe (n = 11) received i.v. injections of saline, epinephrine (EPI) 15 microg; ISO 4, 16, and 80 microg; or epidural (n = 9 ewes) injections of saline, ISO 4 microg and ISO 40 microg. All variables returned to baseline between experiments. Sections of lumber spinal cord were harvested from five animals for later histopathological study. I.v. ISO caused a dose-related increase in MHR. Cardiac output also increased transiently after all doses of ISO but not after EPI. Maternal diastolic blood pressure decreased after ISO 16 and 80 microg. UBF decreased significantly for 120 s after EPI 15 microg. Epidural ISO did not significantly change maternal systemic or pulmonary blood pressure, cardiac output, or UBF. The 40-microg dose increased MHR significantly. No histopathological changes were seen in three ISO-exposed and two control spinal cords. I.v. ISO reliably induces maternal tachycardia in nonstressed gravid ewes. Unlike EPI, I.v. ISO lacks a statistically significant effect on UBF. However, ISO seems to be rapidly absorbed from the epidural space. Identifying the source of maternal tachycardia after epidural injection of a large dose of ISO could be difficult. If the absence of histopathological change is confirmed, ISO represents an alternative to EPI as a chronotropic test dose.

Nifedipine or verapamil counteracts hypertension in gravid ewes.

Hypertension frequently complicates endotracheal intubation in the severely preeclamptic parturient. The calcium entry-blocking drugs nifedipine (N) and verapamil (V) are effective antihypertensive agents in nonpregnant patients. The authors studied the maternal and fetal hemodynamic effects of these drugs in chronically instrumented gravid ewes made hypertensive with an infusion of norepinephrine (NE). Initially NE was infused to increase maternal mean arterial pressure (MAP) by 20%. The NE infusion was continued and either N, 2 mg, or V, 10 mg, was administered intravenously. MAP decreased promptly to control values following both drugs. Maternal heart rate (MHR) decreased significantly following NE infusion. MHR returned to control values following V administration, and increased significantly above control following N administration. Uterine blood flow decreased 50-60% during NE infusion, and there was no further change following either N or V. Fetal hemodynamics were unchanged throughout the study. These results suggest that both N and V may be effective antihypertensive agents in the parturient. V did not produce maternal tachycardia and may be the preferable drug.

Does continuous intravenous infusion of low-concentration epinephrine impair uterine blood flow in pregnant ewes?

BACKGROUND AND OBJECTIVES: Bolus intravenous injection of epinephrine can decrease uterine blood flow. This study examined the effects of intravenous infusion of epinephrine on uterine blood flow in the gravid ewe. METHODS: Maternal and fetal vascular catheters and a maternal electromagnetic uterine artery flow probe were implanted in 10 near-term gravid ewes. After recovery, saline, 0.125% bupivacaine, 0.125% bupivacaine with 1:200,000 epinephrine, 0.125% bupivacaine with 1:400,000 epinephrine, and 0.125% bupivacaine with 1:800,000 epinephrine were infused into the maternal superior vena cava. Drugs were infused at 10 mL/h for 30 minutes and then at 20 mL/h for an additional 30 minutes. Animals also received an intravenous bolus of epinephrine 15 micrograms. Throughout all infusions, maternal heart rate, systemic and pulmonary blood pressures, uterine blood flow, cardiac output, and acid-base balance were measured, as well as fetal heart rate, blood pressure, and acid-base balance. RESULTS: Epinephrine 15 micrograms decreased uterine blood flow to 68 +/- 14% of baseline (mean +/- SD). Infusion of all solutions had no effect on any measured hemodynamic variable. CONCLUSIONS: In gravid ewes, intravenous infusion of < or = 1.67 micrograms/min epinephrine altered neither maternal hemodynamics nor uterine blood flow. To the extent that sheep data can be extrapolated to humans, these results suggest that continuous intravenous infusion of epinephrine in local anesthetic solutions is safe if the epidural catheter should enter a blood vessel during the infusion.