SPINE Volume 39, Number 1, pp 17-22 ©2013, Lippincott Williams & Wiikins
RANDOMIZED TRIAL
Anxiolytic Medication As an Adjunct to Morphine Analgesia for Acute Low Back Pain Management in the Emergency Department A Prospective Randomized Trial Eyal Behrbalk, MD,*t Pinchas Halpern, MD,* Bronek M. Boszczyk, PD Dr. Med,t Ruth M. Parks, MBBS,t Ofir Chechik, MD,* Noam Rosen, MD,* Amir Shapira, MD,* Omri Merose, MD,* and Ofir Uri, MD*
Study Design. Prospective, single-blinded, and randomized clinical trial. Objective. This study evaluates the added benefit of promethazine administration as an anxiolytic adjunct to morphine analgesia in reducing acute low back pain (LBP) compared with morphine alone. Summary of Background Data. Acute LBP is one of the most common reasons for emergency department (FD) visits. The optimal analgesic treatment for acute LBP remains controversial. Anxiety relief has been shown to improve pain management in the ED setting. We hypothesized that administration of the antihistamine promethazine as an anxiolytic adjunct to morphine analgesia will improve LBP management compared with morphine alone. Methods. Fifty-nine adults, who were treated in our FD for severe acute LBP (visual analogue scale & 70 mm), were randomly enrolled in the study. Thirty patients received slow infusion of intravenous (IV) morphine 0.1 mg/kg in normal saline and 29 patients received an analgesic regimen of IV morphine 0.1 mg/kg with promethazine 25 mg administered similarly. Pain and anxiety levels were subjectively assessed by the patients on a 100-mm visual analogue scale before and after treatment. Adverse event related to analgesia were recorded in real time. Results. After analgesia administration patients' pain rating decreased by 43 mm in the morphine group and by 39 mm in the morphine/promethazine group (P = 0.26). Similarly, patients' From the *Orthopedics Division, Tel-Aviv Sourasky Medical Center, TelAviv, Israel; +The Spine Unit, Queen's Medical Centre, Nottingham, United Kingdom; and ^Department of Emergency Medicine, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel. Acknowledgment date: April 22, 2013. First revision date: July 29, 2013. Acceptance date: September 16, 2013. The manuscript submitted does not contain information about medical device(s)/drug(s). No funds were received in support of this work. No relevant financial activities outside the submitted work. Address correspondence and reprint requests to Eyal Behrbalk, MD,The Spine Unit, Queen's Medical Centre, Derby Rd, Nottingham, NC7 2UH, United Kingdom; E-mail: [email protected] DOi: 10.1097/BRS.000Ü000000000038 Spine
anxiety decreased by 19 mm in the morphine group and by 13 mm in the morphine/promethazine group {P = 0.37). The average ED stay was 78 minutes longer in the morphine/promethazine group (P = 0.01 ), due to the strong sedative effect of promethazine. Patients' satisfaction and the rate of adverse events were similar in both groups. Conclusion. IV administration of morphine-promethazine regimen for pain and anxiety relief associated with acute LBP showed no advantage compared with IV morphine alone and significantly lengthened the overall ED stay. Thus, we think that promethazine has no place in acute LBP management in the adult FD setting. Key words: low back pain, pain management, analgesia protocol, morphine, promethazine, anxiolysis, emergency department. Level of Evidence: 1 Spine 2014;39:17-22
A
cute low back pain (LBP) is a common problem in tbe emergency department (ED).' Pain relief is usually the first step in patients' management and enhances early rehabilitation and recovery.^ Numerous medication options are available for acute LBP relief {e.g., NSAIDs, opioids, benzodiazepines, corticosteroids, antidepressants). Each class of medication has its associated benefits and harms and controversy remains regarding the optimal analgesic treatment.^ ** Anxiety has been associated with increased pain intensity in patients with acute LBP, and anxiolysis by nonpharmacological measures (e.g., environmental, psychological, reassurance) has been found to have a positive effect on pain management in the ED setting.'''" Antihistamines have a strong anxiolytic-sedative effect and have been safely and effectively used in managing pain and anxiety associated with various medical procedures.''-'- Antihistamines have also been reported to enhance morphine's analgesic effect.''''"* Promethazine (i.e., a first-generation antihistamine of the phenothiazine chemical class) has been reported to relieve pain and anxiety in labor'' and to reduce anxiety associated with dental procedures." The use of www.spinejournal.com
17
RANDOMIZED TRIAL
antihistamine medication as an adjunct to analgesia for acute LBP and anxiety relief in the ED has not been previously evaluated to the best of our knowledge. The objective of this study was to evaluate the effectiveness of promethazine as an adjunct to morphine analgesia compared with morphine alone, for acute LBP and anxiety relief in the adult FD setting. We hypothesized that promethazine, due to its strong anxiolytic properties, will improve LBP management in the stressful ED environment.
MATERIALS AND METHODS Study Design and Setting This prospective, single-blinded, randomized clinical trial was conducted in the adult ED of the Tel-Aviv Sourasky Medical Center. Patients who were managed in the ED for acute LBP were enrolled from June 2010 to May 2011 as a convenience sample based on the availability of the first author (who was in charge of enrollment and randomization of patients) during all hours of the day and all days of the week. The study was approved by the Institutional Ethics Committee (registered at CIinicaltrials.gov as NCTOl 129934) and informed consent was obtained from all subjects.
Selection of Participants All patients with acute LBP who were treated in the ED were candidates for inclusion in the study. The inclusion criteria were: (1) acute LBP {i.e., less than 3-wk duration); (2) no "red flag" signs that may suggest serious spinal pathology {e.g., history of trauma, malignancy, fever, weight loss, neurological deficit, and bladder or bowel dysfunction)"^; (3) normal neurological examination; (4) eligibility for opioid analgesia based on our ED pain management protocol (i.e., subjective pain rating >70 mm on a 100-mm visual analogue scale [VAS]); (5) an age of 18 to 65 years; (6) American Society of Anesthesiologists score of 1 or 2; (7) systolic blood pressure more than 90 mmHg before administration of analgesia; (8) no known hypersensitivity to the medication used; and (9) willingness and ability to provide an informed consent. Pregnant females and patients who did not meet the study inclusion criteria were excluded from the study.
Study Protocol Detailed medical history was obtained from each patient followed by a thorough physical examination. Patients who met all inclusion criteria and requested analgesia were informed about the benefits and risks of analgesia with morphine and morphine-promethazine regimen. After providing signed informed consent, each patient was randomized to receive either (1) intravenous (IV) morphine (0.1 mg/kg or up to 10 mg) administered slowly in a 150 mL normal saline infusion for 30 minutes or (2) IV morphine (0.1 mg/kg or up to 10 mg) with promethazine 25 mg administered similarly in a single infusion. Randomization was achieved by opening consecutively numbered envelopes containing equal numbers of morphine and morphine/promethazine assignments (prepared by personnel not directly involved in the study). The treating 18
www.spinejournal.com
LBP Management in the ED • Behrbalk et al
physician who prescribed the medication (after randomization) and the registered nurse who administered the analgesic infusion were aware of the group assignment. The patients, however, remained blinded to the medication they received. Vital signs {i.e., heart rate, blood pressure, blood oxygen saturation) were monitored continuously during analgesia administration and afterward in patients who became drowsy. Drowsiness was defined by modified Ramsay sedation scale {i.e., 1, patient awake and oriented may be anxious, agitated, or both; 2, patient awake cooperative, oriented, and tranquil; 3, patient awake but drowsy, responds to commands only; 4, patient asleep, brisk response to light glabellar tap; 5, patient asleep, sluggish response to light glabellar tap; 6, patient asleep with no response).'' Vital signs and modified Ramsay level were dociunented in the patients' medical records before the initiation of analgesia, every 10 minutes until the analgesic infusion was completely administered and then every 30 minutes for additional 2 hours (or until return the modified Ramsay level I). Major adverse events were recorded in real time and included: (1) apnea {i.e., the absence of breathing for 20 s or more); (2) hypoxemia {i.e., an 02Sat of
RANDOMIZED TRIAL
Anxiolytic Medication As an Adjunct to Morphine Analgesia for Acute Low Back Pain Management in the Emergency Department A Prospective Randomized Trial Eyal Behrbalk, MD,*t Pinchas Halpern, MD,* Bronek M. Boszczyk, PD Dr. Med,t Ruth M. Parks, MBBS,t Ofir Chechik, MD,* Noam Rosen, MD,* Amir Shapira, MD,* Omri Merose, MD,* and Ofir Uri, MD*
Study Design. Prospective, single-blinded, and randomized clinical trial. Objective. This study evaluates the added benefit of promethazine administration as an anxiolytic adjunct to morphine analgesia in reducing acute low back pain (LBP) compared with morphine alone. Summary of Background Data. Acute LBP is one of the most common reasons for emergency department (FD) visits. The optimal analgesic treatment for acute LBP remains controversial. Anxiety relief has been shown to improve pain management in the ED setting. We hypothesized that administration of the antihistamine promethazine as an anxiolytic adjunct to morphine analgesia will improve LBP management compared with morphine alone. Methods. Fifty-nine adults, who were treated in our FD for severe acute LBP (visual analogue scale & 70 mm), were randomly enrolled in the study. Thirty patients received slow infusion of intravenous (IV) morphine 0.1 mg/kg in normal saline and 29 patients received an analgesic regimen of IV morphine 0.1 mg/kg with promethazine 25 mg administered similarly. Pain and anxiety levels were subjectively assessed by the patients on a 100-mm visual analogue scale before and after treatment. Adverse event related to analgesia were recorded in real time. Results. After analgesia administration patients' pain rating decreased by 43 mm in the morphine group and by 39 mm in the morphine/promethazine group (P = 0.26). Similarly, patients' From the *Orthopedics Division, Tel-Aviv Sourasky Medical Center, TelAviv, Israel; +The Spine Unit, Queen's Medical Centre, Nottingham, United Kingdom; and ^Department of Emergency Medicine, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel. Acknowledgment date: April 22, 2013. First revision date: July 29, 2013. Acceptance date: September 16, 2013. The manuscript submitted does not contain information about medical device(s)/drug(s). No funds were received in support of this work. No relevant financial activities outside the submitted work. Address correspondence and reprint requests to Eyal Behrbalk, MD,The Spine Unit, Queen's Medical Centre, Derby Rd, Nottingham, NC7 2UH, United Kingdom; E-mail: [email protected] DOi: 10.1097/BRS.000Ü000000000038 Spine
anxiety decreased by 19 mm in the morphine group and by 13 mm in the morphine/promethazine group {P = 0.37). The average ED stay was 78 minutes longer in the morphine/promethazine group (P = 0.01 ), due to the strong sedative effect of promethazine. Patients' satisfaction and the rate of adverse events were similar in both groups. Conclusion. IV administration of morphine-promethazine regimen for pain and anxiety relief associated with acute LBP showed no advantage compared with IV morphine alone and significantly lengthened the overall ED stay. Thus, we think that promethazine has no place in acute LBP management in the adult FD setting. Key words: low back pain, pain management, analgesia protocol, morphine, promethazine, anxiolysis, emergency department. Level of Evidence: 1 Spine 2014;39:17-22
A
cute low back pain (LBP) is a common problem in tbe emergency department (ED).' Pain relief is usually the first step in patients' management and enhances early rehabilitation and recovery.^ Numerous medication options are available for acute LBP relief {e.g., NSAIDs, opioids, benzodiazepines, corticosteroids, antidepressants). Each class of medication has its associated benefits and harms and controversy remains regarding the optimal analgesic treatment.^ ** Anxiety has been associated with increased pain intensity in patients with acute LBP, and anxiolysis by nonpharmacological measures (e.g., environmental, psychological, reassurance) has been found to have a positive effect on pain management in the ED setting.'''" Antihistamines have a strong anxiolytic-sedative effect and have been safely and effectively used in managing pain and anxiety associated with various medical procedures.''-'- Antihistamines have also been reported to enhance morphine's analgesic effect.''''"* Promethazine (i.e., a first-generation antihistamine of the phenothiazine chemical class) has been reported to relieve pain and anxiety in labor'' and to reduce anxiety associated with dental procedures." The use of www.spinejournal.com
17
RANDOMIZED TRIAL
antihistamine medication as an adjunct to analgesia for acute LBP and anxiety relief in the ED has not been previously evaluated to the best of our knowledge. The objective of this study was to evaluate the effectiveness of promethazine as an adjunct to morphine analgesia compared with morphine alone, for acute LBP and anxiety relief in the adult FD setting. We hypothesized that promethazine, due to its strong anxiolytic properties, will improve LBP management in the stressful ED environment.
MATERIALS AND METHODS Study Design and Setting This prospective, single-blinded, randomized clinical trial was conducted in the adult ED of the Tel-Aviv Sourasky Medical Center. Patients who were managed in the ED for acute LBP were enrolled from June 2010 to May 2011 as a convenience sample based on the availability of the first author (who was in charge of enrollment and randomization of patients) during all hours of the day and all days of the week. The study was approved by the Institutional Ethics Committee (registered at CIinicaltrials.gov as NCTOl 129934) and informed consent was obtained from all subjects.
Selection of Participants All patients with acute LBP who were treated in the ED were candidates for inclusion in the study. The inclusion criteria were: (1) acute LBP {i.e., less than 3-wk duration); (2) no "red flag" signs that may suggest serious spinal pathology {e.g., history of trauma, malignancy, fever, weight loss, neurological deficit, and bladder or bowel dysfunction)"^; (3) normal neurological examination; (4) eligibility for opioid analgesia based on our ED pain management protocol (i.e., subjective pain rating >70 mm on a 100-mm visual analogue scale [VAS]); (5) an age of 18 to 65 years; (6) American Society of Anesthesiologists score of 1 or 2; (7) systolic blood pressure more than 90 mmHg before administration of analgesia; (8) no known hypersensitivity to the medication used; and (9) willingness and ability to provide an informed consent. Pregnant females and patients who did not meet the study inclusion criteria were excluded from the study.
Study Protocol Detailed medical history was obtained from each patient followed by a thorough physical examination. Patients who met all inclusion criteria and requested analgesia were informed about the benefits and risks of analgesia with morphine and morphine-promethazine regimen. After providing signed informed consent, each patient was randomized to receive either (1) intravenous (IV) morphine (0.1 mg/kg or up to 10 mg) administered slowly in a 150 mL normal saline infusion for 30 minutes or (2) IV morphine (0.1 mg/kg or up to 10 mg) with promethazine 25 mg administered similarly in a single infusion. Randomization was achieved by opening consecutively numbered envelopes containing equal numbers of morphine and morphine/promethazine assignments (prepared by personnel not directly involved in the study). The treating 18
www.spinejournal.com
LBP Management in the ED • Behrbalk et al
physician who prescribed the medication (after randomization) and the registered nurse who administered the analgesic infusion were aware of the group assignment. The patients, however, remained blinded to the medication they received. Vital signs {i.e., heart rate, blood pressure, blood oxygen saturation) were monitored continuously during analgesia administration and afterward in patients who became drowsy. Drowsiness was defined by modified Ramsay sedation scale {i.e., 1, patient awake and oriented may be anxious, agitated, or both; 2, patient awake cooperative, oriented, and tranquil; 3, patient awake but drowsy, responds to commands only; 4, patient asleep, brisk response to light glabellar tap; 5, patient asleep, sluggish response to light glabellar tap; 6, patient asleep with no response).'' Vital signs and modified Ramsay level were dociunented in the patients' medical records before the initiation of analgesia, every 10 minutes until the analgesic infusion was completely administered and then every 30 minutes for additional 2 hours (or until return the modified Ramsay level I). Major adverse events were recorded in real time and included: (1) apnea {i.e., the absence of breathing for 20 s or more); (2) hypoxemia {i.e., an 02Sat of
