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Postoperative Analgesia After Spinal Blockade in Infants and Children Undergoing Cardiac Surgery

Hammer, Gregory B. MD; Ramamoorthy, Chandra MBBS*; Cao, Hong MD*; Williams, Glyn D. MD*; Boltz, M Gail MD*; Kamra, Komal MBBS*; Drover, David R. MD*

doi: 10.1213/01.ANE.0000148698.84881.10
Pediatric Anesthesia: Research Report

The aim of this prospective, randomized, controlled clinical trial was to define the opioid analgesic requirement after a remifentanil (REMI)-based anesthetic with spinal anesthetic blockade (SAB+REMI) or without (REMI) spinal blockade for open-heart surgery in children. We enrolled 45 patients who were candidates for tracheal extubation in the operating room after cardiac surgery. Exclusion criteria included age <3 mo and >6 yr, pulmonary hypertension, congestive heart failure, contraindication to SAB, and failure to obtain informed consent. All patients had an inhaled induction with sevoflurane and maintenance of anesthesia with REMI and isoflurane (0.3% end-tidal). In addition, patients assigned to the SAB+REMI group received SAB with tetracaine (0.5–2.0 mg/kg) and morphine (7 μg/kg). After tracheal extubation in the operating room, patients received fentanyl 0.3 μg/kg IV every 10 min by patient-controlled analgesia for pain score = 4. Pain scores and fentanyl doses were recorded every hour for 24 h or until the patient was ready for discharge from the intensive care unit. Patients in the SAB+REMI group had significantly lower pain scores (P = 0.046 for the first 8 h; P =0.05 for 24 h) and received less IV fentanyl (P = 0.003 for the first 8 h; P = 0.004 for 24 h) than those in the REMI group. There were no intergroup differences in adverse effects, including hypotension, bradycardia, highest PaCO2, lowest pH, episodes of oxygen desaturation, pruritus, and vomiting.

IMPLICATIONS: The addition of spinal anesthesia with tetracaine and morphine to a remifentanil-based general anesthetic resulted in satisfactory analgesia without increasing the incidence of adverse effects in pediatric patients anesthetized with remifentanil and isoflurane during open-heart surgery.

Departments of *Anesthesia and §Pediatrics, Stanford University Medical Center, California

Supported, in part, by a grant from Physiometrix, Inc., N. Billerica, MA.

Accepted for publication October 11, 2004.

Address correspondence and reprint requests to Gregory B. Hammer, MD, Department of Anesthesia, Room H3580, Stanford University Medical Center, 300 Pasteur Dr., Stanford, CA 94305-5115. Address e-mail to

Early tracheal extubation after cardiac surgery (fast-track anesthesia) is becoming common practice in adult patients and has also been described in infants and children (1–4). Tracheal extubation in the operating room (OR) after the completion of surgery obviates the need for postoperative mechanical ventilation, avoiding associated costs and potential complications such as malpositioning of the endotracheal tube, excessive tracheobronchial secretions, and pulmonary hypertensive response to tracheal suctioning. Because of its very short duration of action, remifentanil (REMI) has been used during cardiac surgery to provide the benefits of a large-dose opioid anesthetic (e.g., minimal sympathetic response to tracheal intubation and sternotomy) while allowing tracheal extubation in the OR. However, because of its short duration of action, REMI does not provide postoperative analgesia. Strategies for postoperative analgesia include use of longer-acting IV opioids before or shortly after emergence from general anesthesia or regional anesthesia.

The use of regional anesthesia in combination with general anesthesia for adult patients undergoing cardiac surgery is well documented. A multinational survey (1) reported that approximately 8% of practicing cardiac anesthesiologists use spinal anesthetic techniques routinely in adult patients undergoing open-heart surgery to facilitate early tracheal extubation. IV REMI anesthesia and intrathecal (IT) morphine have been used for fast-track anesthesia because these drugs provide the benefits of rapid emergence as well as postoperative analgesia (2,3). There have been no published reports comparing the postoperative opioid analgesic requirements after the use of REMI with or without spinal anesthesia blockade (SAB). We performed this prospective, randomized, controlled clinical trial to evaluate the effects on postoperative analgesia of IT tetracaine and morphine in children undergoing open-heart surgery with a REMI-based anesthetic technique and scheduled tracheal extubation in the OR after surgery (fast-track anesthesia).

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After IRB approval and written informed parental consent were obtained, 45 infants and children undergoing open-heart surgery were enrolled in this study. Inclusion criteria were age 3 mo to 6 yr and planned tracheal extubation in the OR after surgery. Exclusion criteria were significant pulmonary hypertension (i.e., likely to require treatment after surgery), severe congestive heart failure, contraindication to SAB, and failure to obtain informed consent.

Patients were randomly assigned to receive either SAB with tetracaine and morphine in addition to a continuous infusion of REMI and isoflurane (SAB+REMI group) or REMI and isoflurane without SAB (REMI group). In the SAB+REMI group, spinal tetracaine and morphine were administered according to our previously published dosing regimen (4) (Table 1). Patients in both groups were premedicated with oral midazolam 0.5–0.75 mg/kg, as deemed appropriate by the anesthesiologist. After placement of routine monitors, all patients underwent an inhaled induction with sevoflurane in N2O/O2, after which an IV catheter was inserted. Rocuronium 1.0 mg/kg IV was administered, and tracheal intubation was performed.

Table 1

Table 1

Patients were then turned to the right lateral decubitus position for SAB and bandage placement (SAB+REMI group) or bandage placement only (REMI group). SAB was administered via a 25-gauge Quincke needle inserted at L3-4 or L4-5.

Patients were then placed in the Trendelenburg position for insertion of central venous and arterial catheters. Once all vascular access catheters were placed, sevoflurane was discontinued, and isoflurane (0.3% end-tidal) was administered in air/O2 for maintenance of anesthesia. A continuous infusion of REMI was initiated using a target-controlled infusion system. The target-controlled infusion system uses the program Rugloop1, and the REMI population variables, as previously determined, were programmed into the software (5). The REMI was titrated by the anesthesiologist to a predicted plasma concentration of 1–8 ng/mL according to hemodynamic signs of the depth of anesthesia until the completion of surgery (i.e., including cardiopulmonary bypass [CPB]). During CPB, the isoflurane was initially continued at an end-tidal concentration of 0.3% and was increased as required if the REMI was at the maximum infusion rate of 8 ng/mL and the mean arterial blood pressure was increased. Isoflurane was maintained at an end-tidal concentration of 0.3% after separation from CPB. Additional doses of rocuronium were administered to maintain neuromuscular blockade. Isoflurane was discontinued with the beginning of skin closure, and 100% oxygen was administered at a fresh gas flow of 10 L/min. The REMI infusion was discontinued upon completion of skin closure, and residual neuromuscular blockade was antagonized with neostigmine 0.07 mg/kg and glycopyrrolate 0.01 mg/kg. Tracheal extubation was performed after spontaneous respirations, eye opening, and demonstration of adequate motor tone.

After tracheal extubation in the OR, all patients received fentanyl 0.5 μg/kg IV incrementally as required to achieve a pain score <4. Postoperative pain was assessed in the OR and cardiovascular intensive care unit (CVICU) using the Face, Legs, Activity, Cry, and Consolability (FLACC) Postoperative Pain Measurement Scale for patients <3 yr of age and the Wong-Baker Faces Scale for patients 3 yr of age (6,7). Patients were transported to the CVICU with supplemental oxygen via face mask with continuous hemodynamic monitoring and pulse oximetry.

Blood samples were collected from each patient shortly after arrival in the CVICU for arterial blood gas (ABG) tension analysis. The timing of subsequent ABGs was determined by the CVICU service; a minimum of five samples were analyzed for each patient during the study period. Postoperative pain assessment was performed by the bedside CVICU nurse, who was blinded to the treatment group. Fentanyl 0.3 μg/kg IV was administered by the CVICU nurse via a patient-controlled analgesia device (Abbott Lifecare 4100, Abbott Laboratories, North Chicago, IL) with a lockout interval of 8 min whenever the pain score was 4. No other analgesics were administered during the study period, which continued until the earlier of either discharge from the CVICU or 24 h after CVICU admission. Supplemental therapy included midazolam 0.025–0.05 mg/kg IV for anxiety, diphenhydramine 0.5–1.0 mg/kg IV for severe pruritus, and ondansetron 0.1 mg/kg IV as required for nausea or vomiting documented by the CVICU nurse.

Vital signs, oxygen saturation, rectal temperature, pain scores, and fentanyl doses were recorded every hour during the study period. Episodes of clinically significant bradycardia and hypotension (heart rate and mean arterial blood pressure <80% of baseline) and oxygen desaturation (Spo2 <90% of baseline) were recorded. All doses of supplemental medication, e.g., midazolam, diphenhydramine, and ondansetron, and the results of ABGs were also recorded.

Variables included median pain score over successive 8-h periods and cumulative doses of fentanyl administered (μg/kg every 8 h). The cumulative fentanyl dose during the first 8 h included fentanyl given in the OR after tracheal extubation, as well as that given during the first 8 h in the CVICU. Fentanyl dose during the first 24 h was expressed as the average cumulative dose per 8-h period. The difference in pain score between groups was the primary end-point of the study and the end-point for which the power analysis was performed. With a type I error of 0.05 and power of 80%, we anticipated a minimum difference of 2 in the pain score. The prospective calculation of sample size indicated 20 subjects per group were required, and we planned to replace the subjects who did not complete the protocol. The incidence of treatment for itching, vomiting, and anxiety, as well as lowest pH and highest Paco2 values, were compared. Data were analyzed using the Statistical Package for Social Science (version 11.0 for Windows, SPSS, Chicago, IL). Nonparametric data were analyzed by the Mann-Whitney U- test. A P value <0.05 was considered statistically significant.

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Forty patients completed the study (20 in each group). Two patients in the SAB+REMI group and three in the REMI group were withdrawn from the study because of the decision to continue mechanical ventilation in the CVICU secondary to hypothermia or residual neuromuscular blockade. Both groups were similar with respect to demographics, type of surgery, duration of CPB, and CVICU and hospital lengths of stay (Table 2).

Table 2

Table 2

Median (25%–75% interquartile range [IQR]) pain scores for the first 8 h after surgery were 2.0 (0.0–4.0) and 4.0 (2.0–5.9) in the SAB+REMI and REMI groups, respectively (P = 0.046). Median pain scores for the first 24 h after surgery were 1.5 (0.0–3.8) and 4.0 (0.5–5.0) in the SAB+REMI and REMI groups, respectively (P = 0.05) (Fig. 1).

Figure 1

Figure 1

The median (IQR) fentanyl dose administered for the first 8 h after surgery was 1.7 (0.2–5.4) μg/kg every 8 h and 5.1 (3.9–9.1) μg/kg every 8 h in the SAB+REMI and REMI groups, respectively (P = 0.003). The median (IQR) fentanyl administration for the first 24 h after surgery was 2.1 (0.5–3.2) μg/kg every 8 h and 3.9 (2.8–7.3) μg/kg every 8 h in the SAB+REMI and REMI groups, respectively (P = 0.004) (Fig. 2). The total dose of midazolam administered for anxiety was similar in both groups (Table 3).

Figure 2

Figure 2

Table 3

Table 3

There were no differences between groups with respect to opioid-related adverse effects during the study, including highest Paco2, lowest pH, and episodes of oxygen desaturation, pruritus, and vomiting. No patient in the SAB+REMI group developed bradycardia or hypotension after SAB (i.e., before CPB). No patient in either group developed bradycardia or hypotension in the postoperative period, and no patient received inotropic therapy other than dopamine (maximum dose 5 μg · kg−1 · min−1).

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We previously reported the results of a retrospective study of spinal versus epidural anesthesia in children undergoing open-heart surgery (1–4). This prospective, randomized, controlled clinical trial was a follow-up study performed to characterize the postoperative fentanyl requirements after a REMI-based general anesthetic with and without SAB. As has been the practice in our CVICU, fentanyl was used to provide postoperative analgesia because of its relatively rapid onset. We found that the addition of IT morphine and tetracaine to a REMI-based general anesthetic was associated with satisfactory postoperative analgesia in infants and children undergoing cardiac surgery. As anticipated, patients receiving SAB required less fentanyl and had lower pain scores during the postoperative study period than those in the control group. In addition, SAB was not associated with adverse hemodynamic, respiratory, or other adverse effects compared with controls.

The use of IT anesthesia in patients undergoing cardiac surgery was initially reported by Mathews and Abrams (8). This and the majority of subsequent publications describing IT anesthesia for cardiac surgery describe the use of IT opioids alone and report effective postoperative analgesia as a primary end-point in adult patients (2,3,9,10). Kowalewski et al. (11) published a retrospective report of the use of a combination of IT local anesthetic (hyperbaric bupivacaine or lidocaine) and morphine (0.5–1.0 mg) in adults undergoing cardiac surgery (12). The authors attempted to produce thoracic cardiac sympathectomy by maintaining the Trendelenburg position for at least 10 minutes after IT injection. Although the authors reported stable perioperative hemodynamics, 17 of 18 patients received phenylephrine during surgery.

Unlike adults, young children do not seem to develop bradycardia and hypotension after high SAB with local anesthetics. Finkel et al. (12) evaluated hemodynamic changes during high SAB in children having open-heart surgery. After administration of IT hyperbaric tetracaine and morphine, all patients were kept in a steep Trendelenburg position to maximize cephalad spread of the SAB. Hemodynamic stability was demonstrated in all patients without clinically significant changes in either heart rate or arterial blood pressure attributable to the SAB. All patients underwent tracheal extubation shortly after completion of surgery. This supports previous reports that local anesthetic blockade to T3-5 does not produce significant changes in arterial blood pressure or heart rate in infants and young children (4,13). This may be attributable to decreased sympathetic innervation of the lower extremities or immaturity of the sympathetic nervous system in young children.

Pirat et al. (14) compared cardiovascular and neurohumoral responses associated with IT or IV fentanyl in pediatric patients undergoing cardiac surgery. Thirty patients were randomly assigned to receive IV fentanyl 10 μg/kg followed by an IV fentanyl infusion (10 μg · kg−1 · h−1), IT fentanyl 2 μg/kg, or a combination of IV and IT fentanyl. Patients receiving both IV and IT fentanyl had less hemodynamic response to sternotomy than those in either of the other groups.

A previous study from this institution compared SAB and epidural anesthesia and postoperative analgesia in pediatric patients having open-heart surgery (4). Patients in the SAB group received a combination of IT morphine (7 μg/kg) and tetracaine (0.5–2.0 mg/kg) after tracheal intubation. All patients were tracheally extubated in the OR immediately after the completion of surgery. Both SAB and epidural anesthesia were associated with circulatory stability, satisfactory postoperative analgesia, and an infrequent incidence of adverse effects. No significant differences between groups were noted in the incidence of clinically significant changes in vital signs, oxygen desaturation, respiratory depression, or vomiting.

Dose-dependent respiratory depression may be seen in children after the administration of IT opioids. Doses of IT morphine of 20 or 30 μg/kg may result in significant respiratory depression after cardiac surgery in children (15). However, in a review of children given IT morphine in a dose of 20 μg/kg in whom no IV opioids were administered during surgery, no patient had postoperative respiratory depression (16). In addition, no child required supplemental opioid analgesia for at least 15 hours after surgery. In a study comparing IT morphine in doses of 5, 7, and 10 μg/kg in children having open-heart surgery, all patients were successfully tracheally extubated at the conclusion of surgery; no patient had signs of respiratory depression.2 In this study, we found that patients in the SAB+REMI group had only mild respiratory depression that was comparable to that seen in the REMI group.

Epidural hematoma formation after SAB is a rare but potentially catastrophic complication of neuraxial blockade in patients receiving anticoagulant therapy. In an analysis of 20 studies, including more than 650,000 cases of SAB in adult patients, Tryba (17) estimated the risk of epidural hematoma after SAB to be 1:220,000. This analysis included an unknown number of patients with clotting abnormalities before spinal needle placement. Taylor et al. (18) reported the use of IT morphine in more than 10,000 patients undergoing cardiac surgery, many of whom were receiving warfarin or aspirin before the admission, without a single case of epidural hematoma. We believe that the use of a 25-gauge spinal needle inserted at L3-4 or L4-5 approximately one hour before administration of heparin in patients with no history of abnormal bleeding presents minimal risk of epidural hematoma.

The use of REMI during cardiac surgery has been described in numerous reports. The rapid onset and short duration of action despite large doses make REMI well suited for intense blockade of sympathetic responses to tracheal intubation and surgery, whereas allowing for the possibility of tracheal extubation in the OR or within a short period of time thereafter (19–23). In adult patients undergoing coronary artery bypass grafting, REMI is associated with stable hemodynamics and rapid emergence from anesthesia (19–24). In patients with severely reduced left ventricular function, REMI provides stable hemodynamics during the induction and maintenance of anesthesia (25). Elliot et al. (26) investigated the effects of a bolus administration of REMI 1 μg/kg administered after a steady-state of anesthesia had been achieved and before stimuli such as tracheal intubation. Several patients developed hypotension, and the authors recommended that bolus dosing should not exceed 0.33 μg/kg under these circumstances. The use of REMI for cardiac surgery in children has been associated with a slower heart rate compared with fentanyl, although no treatment was required in any patient (27). No patient in our study developed clinically significant bradycardia or hypotension related to REMI administration.

We conclude that the addition of SAB with tetracaine and morphine to a REMI-based general anesthetic for children undergoing open-heart surgery resulted in satisfactory analgesia without increasing the incidence of side effects, compared with a REMI-based anesthetic without SAB. This technique may be useful as part of a REMI based anesthetic regimen that facilitates early tracheal extubation without compromising patient comfort.

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1 Rugloop is available from Tom De Smet at
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2 Finkel JC, Conran AM, Boltz MG. A comparison of 3 intrathecal morphine doses during spinal anesthesia in children having open heart surgery [abstract]. Anesthesiology 1997;87:A1052.
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