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Risk of Respiratory Arrest After Intrathecal Sufentanil

1997; Lippincott Williams & Wilkins; Volume: 85; Issue: 5 Linguagem: Inglês

10.1097/00000539-199711000-00022

1526-7598

Fazeela Ferouz, Mark C. Norris, Barbara L. Leighton,

Pediatric Pain Management Techniques

Intrathecal (IT) sufentanil provides profound labor pain relief without significant autonomic or motor blockade. Common side effects include pruritus, sedation, and nausea [1]. More serious complications, such as high sensory level, respiratory depression, and apnea, have been reported [2-4]. After observing a respiratory arrest after 10 micro g IT sufentanil, we reviewed six years of labor anesthetics to estimate the frequency of serious complications accompanying IT sufentanil and epidural local anesthetics. Case Report A 17-yr-old, 65-kg, gravida 1, para 0, at 41 weeks' gestation was admitted to our hospital for postdate-induction of labor. Her medical history was unremarkable. On Day 2 of induction, she requested labor analgesia 150 min after receiving intravenous (IV) meperidine 50 mg and hydroxyzine 25 mg. Examination revealed 2.5-cm cervical dilation, 80% effacement, and -2 station. She was alert, with a blood pressure (BP) of 137/67 mm Hg and heart rate (HR) of 75 bpm. Fetal HR was 135-140 bpm with good variability. The patient was enrolled in a clinical study of differing depths of epidural catheter insertion [5]. With the patient in the sitting position, we induced combined spinal/epidural (CSE) analgesia at the L2-3 interspace using sufentanil 10 micro g in a total volume of 3 mL preservative-free normal saline (PFNS). The sufentanil solution was prepared (by FF) by diluting a 1-mL ampule of sufentanil 50 micro g/mL in 4 mL PFNS. One milliliter of this solution was diluted with 2 mL PFNS and injected into a sterile syringe held by the resident performing the procedure. A polyamide catheter was passed 8 cm beyond the tip of the epidural needle and secured. The patient was then positioned supine with left uterine displacement. Simultaneously, we injected 3 mL of 0.25% bupivacaine to detect IT catheter location. A negative air test ruled out intravascular catheter placement [6]. Four minutes after intrathecal sufentanil injection, the patient was very somnolent. Immediately afterward, she was unresponsive to verbal and painful stimuli and then apneic with pinpoint pupils. BP was 107/47 mm Hg, HR was 72 bpm, and fetal HR had decreased to 60 bpm. She was promptly ventilated via a mask with 100% oxygen and cricoid pressure and then tracheally intubated without complication. Both during and after tracheal intubation, she was moving all extremities. The fetal HR remained less than 100 bpm, and the obstetrician decided to perform an emergency cesarean delivery. Surgical anesthesia was provided with 0.2%-0.4% inspired isoflurane in 50% nitrous oxide and 50% oxygen until delivery. A viable female infant was delivered with Apgar scores of 1 at 1 min, 7 at 5 min, and 9 at 10 min. After delivery, the patient was given 10 mg of morphine in divided doses and 70% nitrous oxide and 30% oxygen. BP was 100-120/50-60 mm Hg, and HR varied from 80 to 90 bpm throughout the procedure, which lasted 38 min. On emergence, the patient could move all extremities and had no motor flaccidity or sensory deficits. The obstetrician ordered a computed tomography scan of the head, which was negative. Fluoroscopic examination of the lumbar spine during radiopaque dye injection of the epidural catheter revealed dye confined to the epidural space with no leakage to the subarachnoid or subdural space. Both mother and infant were discharged home after an uneventful remaining hospital course. Retrospective Chart Review This event was the first serious anesthetic-related complication to occur in our obstetric anesthesia service in many years. As a result, we wished to estimate the risk of respiratory arrest with intrathecal sufentanil. We obtained institutional review board approval and tabulated the number of parturients who received neuraxial labor analgesia with IT sufentanil or epidural local anesthetics between July 1990 (date of first use) and June 1996. At Thomas Jefferson University Hospital, every patient who receives a labor anesthetic is recorded in both a logbook and computer spreadsheet. Specifically, we document the patient's name and medical record number, the resident and attending physician performing the procedure, the type of anesthetic, the opioid(s) used, the type of delivery, and any complications. Complications were considered to be any adverse events (i.e., seizure, total spinal, accidental dural puncture, cardiac arrest) that occurred from the time of the anesthetic until the postoperative visit by an attending anesthesiologist 24 h later. During this period, 10,047 parturients received neuraxial analgesia for labor. Of these women, 4,870 received intrathecal sufentanil as a part of a CSE technique. A smaller subgroup (n = 543) received other intrathecal opioids. In most cases, we induced CSE analgesia with 10 micro g of sufentanil in 3 mL of PFNS. Epidural catheters were tested to rule out IT and intravascular placement by injecting 3 mL of 0.25% bupivacaine and performing an air test, respectively. When the sufentanil analgesia waned, we usually injected 8-12 mL of either 0.125% bupivacaine with 10 micro g/mL fentanyl or 0.25% bupivacaine into the epidural catheter. A small number of patients did not require epidural drug injection. The remaining 4,634 women had only epidural drug injection. After testing for IT or intravascular placement, we usually injected 8-12 mL of either 0.125% bupivacaine with 10 micro g/mL fentanyl or 0.25% bupivacaine. Then, an infusion of a 0.05% bupivacaine, 1.45 micro g/mL fentanyl and 1:700,000 epinephrine solution is started at 6-10 mL/h. During this time, the dose and type of epidural local anesthetic and opioid were continually modified to improve the technique. However, none of these patients suffered a serious complication (seizure, total spinal, cardiovascular collapse, respiratory arrest) attributable to epidural local anesthetic or opioid injection. This case was the only respiratory arrest among these 10,047 parturients. Discussion Our patient suffered a sudden respiratory arrest within four minutes of receiving IT sufentanil 10 micro g. Although sufentanil is the most likely cause of this event, other etiologies must be considered. In addition to sufentanil, this patient received 3 mL 0.25% bupivacaine via her epidural catheter. IT or subdural injection of this "test dose" may have produced extensive sensory, motor, and sympathetic blockade [7], but respiratory arrest is unlikely. Furthermore, there were no signs of spinal anesthesia, such as motor flaccidity or hypotension, in this patient, and radiographic examination confirmed epidural catheter location. Movement of the local anesthetic across the meningeal hole created by the 24-gauge Sprotte needle could have potentiated the effect of sufentanil [8]. Clinically, this effect produces a slightly higher dermatomal level of analgesia but not respiratory compromise [9]. The epidural injection of 12 mL of normal saline increases the spread of previously injected IT local anesthetic by two to three dermatomes [10]. Injecting the epidural test dose could have forced the sufentanil further cephalad by a mechanical effect. However, our preparation of IT sufentanil is already hypobaric [11], and thus ascends rapidly to the brainstem [12]. It is unlikely that the epidural injection of such a small volume (3 mL) would have a significant effect on the rostral spread of IT sufentanil. In this patient, we inserted the epidural catheter 8 cm. As a result, we could have injected the bupivacaine test dose higher in the neuraxis than expected. Although a thoracic epidural injection can cause hypotension, it does not cause respiratory arrest. Radiographic analysis of epidural catheters inserted to 8 cm shows that they tend to curl back on themselves [13,14]. Thus, they are not necessarily higher in the neuraxis. In this case, the bupivacaine test dose was injected into the epidural space, and we believe that it did not contribute significantly to the events that followed. Finally, this patient received the first aliquot (1 mL) from a freshly prepared syringe of 5 mL of sufentanil 10 micro g/mL. To rule out inadvertant drug administration or overdose, we sent the remaining sample for analysis. The concentration and composition was confirmed to be sufentanil 10 micro g/mL (Smith-Kline Laboratories, Philadelphia, PA). We also verfied that the appropriate residual volume (4 mL) was in the original syringe. Respiratory depression and apnea have been reported after one 15-micro g [3] and two 12.5-micro g [4] doses of IT sufentanil. In these cases, sufentanil was the sole drug injected, and the onset of symptoms occurred within 30 minutes. Respiratory arrest was recently reported in a patient who received 10 micro g of sufentanil and 2.5 mg of bupivacaine [15]. We used only 10 micro g of sufentanil, but our patient also received meperidine IV 150 minutes before IT sufentanil. Thus, both sufentanil and meperidine may have contributed to the immediate respiratory arrest seen in our patient. Unfortunately, we do not record the systemic analgesics received before neuraxial anesthesia in our logbooks. This interaction deserves further investigation. The commonly used doses of IT sufentanil (10-15 micro g) may be excessive for labor analgesia. Several groups have reported the efficacy of smaller doses of sufentanil.1,2 In a small study, increasing the dose of sufentanil from 5 to 15 micro g neither improved the quality nor prolonged the duration of pain relief [16]. If these data are confirmed in a larger study, it may be prudent to use smaller doses of IT sufentanil. (1) Cooper M, Arkoosh VA, Norris MC, et al. Intrathecal sufentanil dose response in nulliparous patients [abstract]. Anesthesiology 1993;79:A1000. (2) Naulty JS, Barnes D, Becker R, Pate A. Continuous subarachnoid sufentanil for labor analgesia [abstract]. Anesthesiology 1990;73:A964. In our six years of experience with IT sufentanil, the risk of respiratory arrest is 0.021% (1 of 4,870, 95% confidence interval 0%-0.061%). This is the largest series of patients who have received IT sufentanil reported to date. The risk of serious complications after epidural local anesthetics (approximately 0 of 10,047) is 0.0%-0.029% [17]. From our results, we cannot compare the relative safety of IT opiods versus epidural local anesthetics. A study showing that the risk of serious complications is twice as great after IT sufentanil than after epidural local anesthetics would require approximately 215,000 subjects in each group [18]. There may be differences in the risk of serious complications between current techniques of epidural blockade and IT opioids for labor analgesia. Serious complications of epidural blockade can be prevented. Careful clinical practice, including aspiration, test doses, and fractionated injection of local anesthetics, should detect inappropriate IT or IV catheter location before potentially catastrophic doses of a drug are given. In contrast, the risk of respiratory arrest may be intrinsic to our current use of intrathecal opioids. The use of relatively large doses, repeated injections, and previous administration of systemic opioids or sedatives may contribute to this risk. Present practices of labor epidural analgesia have evolved over many years with improved understanding of the risks involved. These changes have resulted in the current, very low incidence of serious complications. However, this report emphasizes the need to monitor the use of IT opioids to improve their efficacy and safety.