Pediatric Anesthesia ISSN 1155-5645
ORIGINAL ARTICLE
Magnesium as an adjuvant for caudal analgesia in children Eun Mi Kim1, Min-Soo Kim2, Seok-Joo Han3, Bong Ki Moon4, Eun Mi Choi1, Eun Ho Kim2 & Jeong-Rim Lee2 1 Department of Anesthesiology and Pain Medicine, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea 2 Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, Korea 3 Department of Pediatric Surgery, Yonsei University College of Medicine, Seoul, Korea 4 Department of Anesthesiology and Pain Medicine, Ajou University School of Medicine, Suwon, Korea
Keywords anesthesia; caudal; magnesium; analgesia; adjuvant; anesthesia Correspondence Prof J.-R. Lee, Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul 120-752, Korea Email: [email protected] Section Editor: Per-Arne Lonnqvist Accepted 23 September 2014 doi:10.1111/pan.12559
Summary Background: There is a need for an adjuvant agent of caudal block that prolongs its duration and improves the analgesic efficacy to fasten functional recovery. Magnesium is an N-methyl-D-aspartate receptor antagonist that functions as an analgesic. This study was aimed to evaluate whether magnesium as an adjuvant for caudal block in children can improve postoperative analgesia and functional recovery. Methods: Eighty children, 2–6 years of age, undergoing inguinal herniorrhaphy, were included in this prospective, randomized, double-blinded study. For caudal block, Group R received ropivacaine 1.5 mgml 1, 1 mlkg 1 and Group RM received the same dose of ropivacaine mixed with 50 mg of magnesium. The Parents’ Postoperative Pain Measure (PPPM) score, analgesic consumption, functional recovery, and adverse effects were evaluated at 6, 24, 48, and 72 h after surgery, as well as daily thereafter until the child showed full functional recovery. Results: The PPPM score after hospital discharge was significantly lower for Group RM than for Group R at all times (P < 0.05). Children in Group RM required less fentanyl for rescue analgesia in the recovery area (16.2% vs 39.5%, P = 0.034) and less oral analgesics after discharge (20.5% vs 52.6%, P = 0.007). The time to return of normal functional activity was shorter in Group RM (P < 0.05). The incidence of adverse effects did not differ between groups. Conclusions: As an adjuvant for caudal analgesia, 50 mg magnesium provided superior quality of analgesia and faster return of normal functional activity than local anesthetic alone in children.
Background As a variety of pediatric operations are now performed on an ambulatory surgery basis, faster recovery to normal function has become a major concern for physicians. To facilitate a quick recovery, analgesia should be effective, uncomplicated, and an appropriate duration for the procedure. Inguinal herniorrhaphy is usually conducted under ambulatory basis, but often requires analgesic medication until the third postoperative day (1). For postoperative © 2014 John Wiley & Sons Ltd Pediatric Anesthesia 24 (2014) 1231–1238
pain control, regional blocks, such as caudal block or ilioinguinal/iliohypogastric nerve block, can be applied in pediatric surgery according to an anesthesiologist’s preference. Caudal analgesia is a commonly used technique for children undergoing inguinal herniorrhaphy. However, there are limits to its analgesic duration, if conducted solely with local anesthetic (2). Thus, there has been much interest in finding an adjuvant agent to prolong the duration and improve the quality of analgesia. Furthermore, most children in previous studies were observed for only 24 h or less after surgery; there is a 1231
E.M. Kim et al.
Magnesium for caudal analgesia in children
need for studies with a sufficient duration of observation (3–5). Additionally, the recovery of functional activity in children having a caudal block with adjuvant agent after surgery has not been reported previously. Magnesium has analgesic properties, which have been attributed to its activity as an N-methyl-D-aspartate (NMDA) receptor antagonist in the central nervous system. Numerous adult studies have proven the effectiveness of epidurally and intrathecally admitted magnesium (6–10). Therefore, it can be expected that magnesium is potentially an appealing adjuvant agent for caudal block in children to prolong the duration of analgesia, enhance the quality of analgesia, and facilitate functional recovery. This study was conducted to evaluate the effects of magnesium as an adjuvant for ropivacaine caudal block in children undergoing inguinal herniorrhaphy. The primary outcome measurement was the number of children who required analgesics after discharge. Additionally, the Parents’ Postoperative Pain Measurement (PPPM) score (11) and the functional activity score (FAS) (12) were examined for at least 72 h postoperatively, until full functional recovery was achieved. Methods This trial was approved by the Severance Hospital Institutional Review Board and registered at clinical trial.org (registration number: NCT01679353). This study was conducted between September 2012 and January 2013. Written informed consent was obtained from the parents of the children. All children who were 2–6 years of age, ASA I and II, and undergoing inguinal herniorrhaphy were eligible for inclusion. The exclusion criteria were as follows: allergy to local anesthetics, bleeding tendency, signs of infection or an anatomic abnormality at the needle insertion site, and current use of calcium channel blockers, analgesics, or medications that may affect the neurologic system. Preparation Using a computer-generated random number table (www.random.org), the children were randomized into two equal groups of 40. Group R received a caudal block of ropivacaine 1.5 mgml 1 and 1 mlkg 1. Group RM received the same dose of ropivacaine mixed with 50 mg of magnesium (Masi 10%, Huons, Seoul, Korea). The pharmaceutical company certified that the magnesium solution did not contain preservatives. One study staff member performed the randomization and prepared the medication in an unlabeled syringe and would not involve in any other aspects of the study. All other 1232
individuals were blinded to the patient’s allocation until the end of the study. Anesthesia and caudal block No children received premedication. General anesthesia was induced with 5–6% sevoflurane inhalation. Each child was monitored throughout anesthesia by continuous pulse oximetry and electrocardiography and noninvasive blood pressure measurements obtained every 5 min. After the child was unconscious, a 24-G intravenous catheter was inserted and an infusion of Hartmann solution was begun at 6 mlkg 1h 1. The airway was maintained using a laryngeal mask airway or I-gel with spontaneous respiration. No opioid or neuromuscular blocking agents were administered during surgery. After anesthetic induction, each child was placed in the left lateral decubitus position and a caudal block was performed by one study staff member (J. R. Lee, Assistant Professor) skilled in the technique. After disinfecting the skin with chlorhexidine with alcohol, the needle insertion site was identified by palpation and the drug was injected into the caudal space through a 22-G short-bevel block needle. The surgical incision was made at least 15 min after the injection. If the incision was accompanied by an increase in the mean arterial pressure or heart rate by more than 20% above preincision values, the caudal block would be deemed a failure, the child would be withdrawn from the study, and the child would be administered 1–2 lgkg 1 fentanyl. Anesthesia was maintained with 0.7–1 minimum alveolar concentration (MAC) of sevoflurane. When the surgery was completed, the supraglottic airway device was removed after the confirmation of regular spontaneous respirations, return of consciousness, and restoration of airway reflexes. The child was subsequently transferred to the postanesthesia care unit (PACU). In the PACU, the Faces Legs Activity Cry Consolability tool (FLACC, 0–10) (13) was assessed at 5-min intervals to determine the degree of postoperative pain. Intravenous 0.5 lgkg 1 fentanyl was administered when the FLACC scale was ≥5 or if the child complained of discomfort or pain. Motor function was assessed using a modified Bromage score (0, no paralysis; 1, able to move legs; and 2, unable to move legs). Emergence agitation was evaluated by Aono’s scale (1, calm; 2, consoled easily; 3, moderate agitation; and 4, severe agitation). Bradycardia and hypotension were defined as decreases of more than 20% of the baseline heart rate or mean arterial pressure, respectively. The incidence of other adverse events, including persistent paresthesia, vomiting, rash, pruritus, sedation, and urinary retention, was recorded. © 2014 John Wiley & Sons Ltd Pediatric Anesthesia 24 (2014) 1231–1238
E.M. Kim et al.
The children were discharged home when they were able to drink, urinate, and walk. Before discharge, the parents were instructed how to answer the PPPM questions (Table S1) (11) and were given acetaminophen syrup for use as a pain medication after discharge. Assessment Early postoperative pain during the hospital stay was assessed using the FLACC tools at 5-min intervals for the first 30 min and at 60, 120, and 180 min after surgery. The time and quantity of fentanyl administered during the hospital stay were recorded. After discharge, a study staff member, who did not know the child’s group allocation, conducted a telephone interview. The interviewer surveyed the PPPM scale, the functional recovery, and the use of analgesics at 6, 24, 48, and 72 h after surgery. Postoperative pain at home was assessed using the PPPM scale that consists of 15 questions requiring a ‘yes’ or ‘no’ answer (yes = 1 point and no = 0 point) (11). A PPPM score ≥6 was considered to represent clinically significant pain, requiring analgesics (11). Parents were instructed to give their child acetaminophen syrup 10 mgkg 1 every 4–6 h regularly. If the children did not complain of any discomfort, played normally, and the PPPM was
ORIGINAL ARTICLE
Magnesium as an adjuvant for caudal analgesia in children Eun Mi Kim1, Min-Soo Kim2, Seok-Joo Han3, Bong Ki Moon4, Eun Mi Choi1, Eun Ho Kim2 & Jeong-Rim Lee2 1 Department of Anesthesiology and Pain Medicine, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea 2 Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, Korea 3 Department of Pediatric Surgery, Yonsei University College of Medicine, Seoul, Korea 4 Department of Anesthesiology and Pain Medicine, Ajou University School of Medicine, Suwon, Korea
Keywords anesthesia; caudal; magnesium; analgesia; adjuvant; anesthesia Correspondence Prof J.-R. Lee, Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul 120-752, Korea Email: [email protected] Section Editor: Per-Arne Lonnqvist Accepted 23 September 2014 doi:10.1111/pan.12559
Summary Background: There is a need for an adjuvant agent of caudal block that prolongs its duration and improves the analgesic efficacy to fasten functional recovery. Magnesium is an N-methyl-D-aspartate receptor antagonist that functions as an analgesic. This study was aimed to evaluate whether magnesium as an adjuvant for caudal block in children can improve postoperative analgesia and functional recovery. Methods: Eighty children, 2–6 years of age, undergoing inguinal herniorrhaphy, were included in this prospective, randomized, double-blinded study. For caudal block, Group R received ropivacaine 1.5 mgml 1, 1 mlkg 1 and Group RM received the same dose of ropivacaine mixed with 50 mg of magnesium. The Parents’ Postoperative Pain Measure (PPPM) score, analgesic consumption, functional recovery, and adverse effects were evaluated at 6, 24, 48, and 72 h after surgery, as well as daily thereafter until the child showed full functional recovery. Results: The PPPM score after hospital discharge was significantly lower for Group RM than for Group R at all times (P < 0.05). Children in Group RM required less fentanyl for rescue analgesia in the recovery area (16.2% vs 39.5%, P = 0.034) and less oral analgesics after discharge (20.5% vs 52.6%, P = 0.007). The time to return of normal functional activity was shorter in Group RM (P < 0.05). The incidence of adverse effects did not differ between groups. Conclusions: As an adjuvant for caudal analgesia, 50 mg magnesium provided superior quality of analgesia and faster return of normal functional activity than local anesthetic alone in children.
Background As a variety of pediatric operations are now performed on an ambulatory surgery basis, faster recovery to normal function has become a major concern for physicians. To facilitate a quick recovery, analgesia should be effective, uncomplicated, and an appropriate duration for the procedure. Inguinal herniorrhaphy is usually conducted under ambulatory basis, but often requires analgesic medication until the third postoperative day (1). For postoperative © 2014 John Wiley & Sons Ltd Pediatric Anesthesia 24 (2014) 1231–1238
pain control, regional blocks, such as caudal block or ilioinguinal/iliohypogastric nerve block, can be applied in pediatric surgery according to an anesthesiologist’s preference. Caudal analgesia is a commonly used technique for children undergoing inguinal herniorrhaphy. However, there are limits to its analgesic duration, if conducted solely with local anesthetic (2). Thus, there has been much interest in finding an adjuvant agent to prolong the duration and improve the quality of analgesia. Furthermore, most children in previous studies were observed for only 24 h or less after surgery; there is a 1231
E.M. Kim et al.
Magnesium for caudal analgesia in children
need for studies with a sufficient duration of observation (3–5). Additionally, the recovery of functional activity in children having a caudal block with adjuvant agent after surgery has not been reported previously. Magnesium has analgesic properties, which have been attributed to its activity as an N-methyl-D-aspartate (NMDA) receptor antagonist in the central nervous system. Numerous adult studies have proven the effectiveness of epidurally and intrathecally admitted magnesium (6–10). Therefore, it can be expected that magnesium is potentially an appealing adjuvant agent for caudal block in children to prolong the duration of analgesia, enhance the quality of analgesia, and facilitate functional recovery. This study was conducted to evaluate the effects of magnesium as an adjuvant for ropivacaine caudal block in children undergoing inguinal herniorrhaphy. The primary outcome measurement was the number of children who required analgesics after discharge. Additionally, the Parents’ Postoperative Pain Measurement (PPPM) score (11) and the functional activity score (FAS) (12) were examined for at least 72 h postoperatively, until full functional recovery was achieved. Methods This trial was approved by the Severance Hospital Institutional Review Board and registered at clinical trial.org (registration number: NCT01679353). This study was conducted between September 2012 and January 2013. Written informed consent was obtained from the parents of the children. All children who were 2–6 years of age, ASA I and II, and undergoing inguinal herniorrhaphy were eligible for inclusion. The exclusion criteria were as follows: allergy to local anesthetics, bleeding tendency, signs of infection or an anatomic abnormality at the needle insertion site, and current use of calcium channel blockers, analgesics, or medications that may affect the neurologic system. Preparation Using a computer-generated random number table (www.random.org), the children were randomized into two equal groups of 40. Group R received a caudal block of ropivacaine 1.5 mgml 1 and 1 mlkg 1. Group RM received the same dose of ropivacaine mixed with 50 mg of magnesium (Masi 10%, Huons, Seoul, Korea). The pharmaceutical company certified that the magnesium solution did not contain preservatives. One study staff member performed the randomization and prepared the medication in an unlabeled syringe and would not involve in any other aspects of the study. All other 1232
individuals were blinded to the patient’s allocation until the end of the study. Anesthesia and caudal block No children received premedication. General anesthesia was induced with 5–6% sevoflurane inhalation. Each child was monitored throughout anesthesia by continuous pulse oximetry and electrocardiography and noninvasive blood pressure measurements obtained every 5 min. After the child was unconscious, a 24-G intravenous catheter was inserted and an infusion of Hartmann solution was begun at 6 mlkg 1h 1. The airway was maintained using a laryngeal mask airway or I-gel with spontaneous respiration. No opioid or neuromuscular blocking agents were administered during surgery. After anesthetic induction, each child was placed in the left lateral decubitus position and a caudal block was performed by one study staff member (J. R. Lee, Assistant Professor) skilled in the technique. After disinfecting the skin with chlorhexidine with alcohol, the needle insertion site was identified by palpation and the drug was injected into the caudal space through a 22-G short-bevel block needle. The surgical incision was made at least 15 min after the injection. If the incision was accompanied by an increase in the mean arterial pressure or heart rate by more than 20% above preincision values, the caudal block would be deemed a failure, the child would be withdrawn from the study, and the child would be administered 1–2 lgkg 1 fentanyl. Anesthesia was maintained with 0.7–1 minimum alveolar concentration (MAC) of sevoflurane. When the surgery was completed, the supraglottic airway device was removed after the confirmation of regular spontaneous respirations, return of consciousness, and restoration of airway reflexes. The child was subsequently transferred to the postanesthesia care unit (PACU). In the PACU, the Faces Legs Activity Cry Consolability tool (FLACC, 0–10) (13) was assessed at 5-min intervals to determine the degree of postoperative pain. Intravenous 0.5 lgkg 1 fentanyl was administered when the FLACC scale was ≥5 or if the child complained of discomfort or pain. Motor function was assessed using a modified Bromage score (0, no paralysis; 1, able to move legs; and 2, unable to move legs). Emergence agitation was evaluated by Aono’s scale (1, calm; 2, consoled easily; 3, moderate agitation; and 4, severe agitation). Bradycardia and hypotension were defined as decreases of more than 20% of the baseline heart rate or mean arterial pressure, respectively. The incidence of other adverse events, including persistent paresthesia, vomiting, rash, pruritus, sedation, and urinary retention, was recorded. © 2014 John Wiley & Sons Ltd Pediatric Anesthesia 24 (2014) 1231–1238
E.M. Kim et al.
The children were discharged home when they were able to drink, urinate, and walk. Before discharge, the parents were instructed how to answer the PPPM questions (Table S1) (11) and were given acetaminophen syrup for use as a pain medication after discharge. Assessment Early postoperative pain during the hospital stay was assessed using the FLACC tools at 5-min intervals for the first 30 min and at 60, 120, and 180 min after surgery. The time and quantity of fentanyl administered during the hospital stay were recorded. After discharge, a study staff member, who did not know the child’s group allocation, conducted a telephone interview. The interviewer surveyed the PPPM scale, the functional recovery, and the use of analgesics at 6, 24, 48, and 72 h after surgery. Postoperative pain at home was assessed using the PPPM scale that consists of 15 questions requiring a ‘yes’ or ‘no’ answer (yes = 1 point and no = 0 point) (11). A PPPM score ≥6 was considered to represent clinically significant pain, requiring analgesics (11). Parents were instructed to give their child acetaminophen syrup 10 mgkg 1 every 4–6 h regularly. If the children did not complain of any discomfort, played normally, and the PPPM was
