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.

Combined spinal-epidural versus epidural labor analgesia.

BACKGROUND: Despite the growing popularity of combined spinal-epidural analgesia in laboring women, the exact role of intrathecal opioids and the needle-through-needle technique remains to be determined. The authors hypothesized that anesthetic technique would have little effect on obstetric outcome or anesthetic complications. METHODS: Data were prospectively collected from 2,183 laboring women randomly assigned to have labor analgesia induced with either 10 microg intrathecal sufentanil with or without 2.0 mg bupivacaine (n = 1,071) or 10 microg epidural sufentanil and 12.5-25.0 mg bupivacaine (n = 1,112). Immediately after induction, a continuous epidural infusion of 0.083% bupivacaine plus 0.3 microg/ml sufentanil was begun in all patients and continued until delivery. Labor was managed by nurses, obstetricians, and obstetric residents who were unaware of the anesthetic technique used. RESULTS: Anesthetic technique lacked impact on our primary outcome: mode of delivery or labor duration. Infants whose mothers were allocated to the combined spinal-epidural group had a slightly higher umbilical artery carbon dioxide partial pressure (54.2 +/- 10.4 vs. 53.2 +/- 10.2 mmHg). However, only achieving at least 5 cm cervical dilation before induction of analgesia and having a cesarean delivery were independent risk factors for elevated umbilical artery carbon dioxide partial pressure. The frequencies of accidental dural puncture, failed epidural analgesia, headache, and epidural blood patch were low and similar in the two groups. CONCLUSIONS: Labor progress and outcome are similar among women receiving either combined spinal-epidural or epidural analgesia. The difference in neonatal outcome appears related to the presence of confounding variables. The combined spinal-epidural technique is not associated with an increased frequency of anesthetic complications. Either technique can safely provide effective labor analgesia.

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.

Does epinephrine improve the diagnostic accuracy of aspiration during labor epidural analgesia?

UNLABELLED: Aspiration reliably detects almost all IV multiorifice epidural catheters. Although a supplemental epinephrine 15-microg test dose may detect the rare IV catheter that does not yield blood on aspiration, false-positive epinephrine responses may cause some women to unnecessarily undergo repeat epidural catheter insertion. We evaluated 532 consecutive eligible patients requesting neuraxial labor analgesia. Patients were excluded if they had a contraindication to epinephrine or if they received intrathecal sufentanil/bupivacaine. Multiorifice catheters were inserted 4-6 cm into the epidural space as part of an epidural (n = 305) or combined spinal-epidural (n = 270) technique. We used aspiration, a lidocaine/epinephrine test dose, and bolus injection or infusion of dilute bupivacaine/sufentanil solutions to systematically determine IV, intrathecal, or epidural catheter location. Aspiration alone detected 47 of 48 intravascular catheters. There were 10 positive epinephrine responses: 2 were true positives, 7 were falsely positive (subsequent local anesthetic injection/infusion produced bilateral sensory change and analgesia), and 1 catheter was removed without further testing. Aspiration detected almost all intravascular catheters. Although the epinephrine test dose did detect one catheter that proved to be in a blood vessel, 87.5% of positive responses occurred in women without intravascular catheters. IMPLICATIONS: Epidural catheters may enter a blood vessel. Many clinicians use epinephrine to detect these catheters. Because aspiration alone detects almost all IV multiorifice catheters in laboring women, a subsequent epinephrine test dose may be unnecessary.

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 effect of maternal position on fetal heart rate during epidural or intrathecal labor analgesia.

OBJECTIVE: This study was designed to determine the relationship between maternal position and the incidence of prolonged decelerations after epidural bupivacaine or intrathecal sufentanil analgesia for labor. STUDY DESIGN: Laboring, healthy, term parturient women, with reassuring fetal heart rate tracings, requesting either epidural (n = 145) or intrathecal (n = 160) analgesia were randomly assigned to lie either supine with measured 30-degree left uterine displacement (n = 136) or in the left lateral decubitus position (n = 145). Patients received either intrathecal sufentanil, 10 microg, or epidural 0.25% bupivacaine, 13 mL. An obstetrician, unaware of patient position or type of anesthesia, examined the fetal heart rate tracings. RESULTS: No demographic differences were noted among the groups. Prolonged decelerations occurred with equal frequency after epidural bupivacaine and intrathecal sufentanil (3.9%). Prolonged decelerations were not related to maternal position. No emergency cesarean deliveries were performed as a result of prolonged decelerations. Prolonged decelerations correlated with the frequency of contractions before induction of analgesia (P < .05). Fewer fetal heart rate accelerations were noted after intrathecal sufentanil than after epidural bupivacaine (P < .005). More ephedrine was used after epidural bupivacaine (P < .001). Patients who received epidural analgesia in the left lateral position were more likely to have an asymmetric block (P < .05). CONCLUSIONS: The risk of prolonged deceleration after epidural bupivacaine or intrathecal sufentanil labor analgesia is unrelated to maternal position or analgesic technique.

The influence of epidural needle bevel orientation on spread of sensory blockade in the laboring parturient.

UNLABELLED: Both asymmetrical sensory blockade and dural puncture are undesirable outcomes of epidural analgesia. Identifying the epidural space with the needle bevel oriented parallel to the longitudinal axis of the patient's back limits the risk of headache in the event of dural puncture. However, rotating the bevel to direct a catheter cephalad may risk dural puncture. We prospectively studied the effects of needle rotation on the success of labor epidural analgesia and on the incidence of dural puncture. One hundred sixty ASA physical status I or II laboring parturients were randomly assigned to one of four groups. The epidural space was identified with the bevel of an 18-gauge Hustead needle directed to the patient's left. It was then rotated as follows: Group 0 = no rotation, final bevel orientation left (n = 39); Group 90 = rotation 90 degrees clockwise, bevel cephalad (n = 43); Group 180 = rotation 180 degrees clockwise, bevel right (n = 36); Group 270 = rotation 270 degrees clockwise, bevel caudad (n = 42). A single-orifice catheter was inserted 3 cm, and analgesia was induced in a standardized fashion. Dural puncture was evenly distributed among the groups (4.4%). There were more dermatomal segments blocked, fewer one-sided blocks, and more patients comfortable at 30 min with the needle bevel directed cephalad. Using a catheter inserted through a needle oriented in the cephalad direction increases the success of epidural analgesia. IMPLICATIONS: This prospective study shows that an epidural catheter inserted through a needle oriented in the cephalad direction increases the success of labor analgesia in the parturient. Carefully rotating the needle cephalad does not increase the risk of dural puncture, intravascular catheters, or failed blocks.

Intrathecal sufentanil dose response in nulliparous patients.

BACKGROUND: Intrathecal sufentanil provides effective analgesia during the first stage of labor. A range of doses has been reported to provide adequate pain relief. This study determined the dose of intrathecal sufentanil that produced acceptable pain relief in 50% of nulliparous patients (ED50) who requested labor analgesia. METHODS: With institutional review board approval, 50 nulliparous patients requesting spinal opioid labor analgesia were enrolled into this prospective, randomized, double-blinded study. Each patient was in spontaneous labor at <5 cm cervical dilation. Patients received one of the following doses of intrathecal sufentanil: 1, 2, 3, 5, or 10 microg in 3 ml preservative-free saline (n = 10 for each dose). Pain, pain relief, hemodynamic, respiratory, and side effect data were collected at times 0, 2, 5, 10, 15, 20, 25, and 30 min. Probit analysis of the number of patients in each group who requested additional pain medicine at 30 min was used to determine the ED50. RESULTS: The groups were demographically similar. The ED50 of intrathecal sufentanil was 1.8 microg (SE, 0.6 microg; 95% CI, 2.96 to 0.54 microg). The incidence of side effects was similar among the groups. CONCLUSIONS: This is the first study to determine the ED50 of intrathecal sufentanil in spontaneously laboring nulliparous patients. As dose-response curves are determined for other labor analgesics, future studies can compare equianalgesic doses or dose combinations.

Labor epidural analgesia without an intravascular "test dose".

BACKGROUND: This study prospectively evaluated the ability of aspiration to detect intravascular placement of multiple-orifice epidural catheters. METHODS: Multiple-orifice, 20-gauge epidural catheters were inserted in 1,029 laboring women. Catheters were observed and aspirated for blood or cerebrospinal fluid before they were tested with 2 ml local anesthetic. If the results of this test were negative (no spinal anesthesia), the authors induced and maintained labor analgesia with a dilute local anesthetic and opioid solution. Patients with bilateral sensory change and effective labor analgesia had a "positive" epidural catheter. Women with unilateral block, inadequate analgesia despite some sensory change or those who delivered before being adequately assessed had "equivocal" catheters. Patients with neither analgesia nor sensory change had "negative" catheters. RESULTS: Aspiration and observation identified 60 intravenously placed catheters. Six catheters, which were placed initially in a blood vessel, were withdrawn until aspiration was negative, and then the anesthetic was infused. Four of these catheters were positive and two were still positioned intravascularly. Two other catheters may have been intravenously placed despite negative results of aspiration. The incidence of false-negative results of aspiration was 0 to 2 of 1,085 (upper limit of 95% CI, 0.2% to 0.4%). No patient showed any signs or symptoms of local anesthetic toxicity. CONCLUSIONS: Under the conditions of this study, which include using multiple-orifice catheters and dilute solutions of local anesthetic and opioid, aspiration and incremental drug injection alone safeguard against the risks of intravenously positioned local anesthetics. These results should not be extrapolated to other clinical settings without further study.

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.

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.

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.

Baricity, needle direction, and intrathecal sufentanil labor analgesia.

BACKGROUND: Intrathecal sufentanil relieves labor pain but centrally mediated side effects are common. Preventing rostral spread of intrathecal sufentanil should limit these side effects. Both direction of the lateral opening of a pencil-point needle and drug baricity modify the spread of intrathecal local anesthetics. This randomized, prospective, double-blind study examines the effects of these variables on intrathecal sufentanil labor analgesia. METHODS: Forty laboring, full-term parturients, whose cervixes were dilated less than 5 cm and who requested analgesia for labor were enrolled. Combined spinal epidural analgesia was induced in patients in the sitting position. They were allocated to receive 10 micrograms intrathecal sufentanil diluted with either normal saline or dextrose with the aperture of the pencil-point needle directed cephalad or caudad during drug injection. Thus there were four groups of ten patients: dextrose up, dextrose down, saline up, and saline down. Sufentanil was diluted with normal saline to a concentration of 10 micrograms/ml. The study drug was made by mixing 1 ml sufentanil solution with either 1 ml 10% dextrose or 1 ml normal saline. Visual analog scores for pain, pruritus, nausea, and pain relief were recorded before and 5, 10, 15, and 30 min after drug injection. RESULTS: Baricity, but not needle orientation, influenced pain relief and pruritus. Sufentanil in dextrose produced less itching but also less analgesia. Nine of 20 women in the dextrose groups compared with 1 of 20 in the saline groups requested additional analgesia by 30 min. CONCLUSIONS: Little or no labor analgesia developed for patients receiving sufentanil with dextrose. A supraspinal action may contribute to intrathecal sufentanil's analgesic efficacy.

The dermatomal spread of epidural bupivacaine with and without prior intrathecal sufentanil.

Clinicians often use a technique combining intrathecal sufentanil and epidural bupivacaine to provide labor analgesia. This study determines the effect of 27- or 24-gauge dural puncture and intrathecal sufentanil 10 micrograms on the dermatomal spread of epidural bupivacaine. Healthy laboring women received no dural puncture (n = 77) (no puncture group [NPG]) or dural puncture with a 27-gauge Whitacre needle (n = 33) or a 24-gauge Sprotte needle (n = 37) and intrathecal sufentanil 10 micrograms (dural puncture group [DPG]) before epidural injection of 13 mL bupivacaine 0.25%. More dermatomes were anesthetized in the DPG, 16.6 +/- 7.5 vs 13.6 +/- 6.6 in the NPG (P < 0.02). More patients in the DPG had sensory blockade T-4 or higher (17 of 70 DPG patients vs 8 of 77 NPG patients; P < 0.05). No patient in either group showed clinical evidence of respiratory compromise. In conclusion, epidural bupivacaine anesthetized more dermatomes when administered 104 +/- 42 min after dural puncture and intrathecal sufentanil 10 micrograms than when given without prior dural puncture and intrathecal injection.

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.