CASE REPORT fentanyl, infusion
Continuous Intravenous Infusion Fentanyl for Sedation and Analgesia of the Multiple Trauma Patient Fentanyl is an attractive agent for analgesia in the emergency department. Its use in this setting has been limited to IV bolus administration. We report successful sedation, muscle relaxation, and analgesia of a multiple trauma patient with fentanyl IV bolus and continuous infusion in the ED. [Walsh M, Smith GA, Yount RA, Ferlic FJ, Wieschhaus MF: Continuous intravenous infusion fentanyl for sedation and analgesia of the multiple trauma patient. Ann Emerg Med August 1991;20:913-915.] INTRODUCTION Fentanyl is a synthetic narcotic analgesic that has a potency 150 times that of morphine.l Because of its rapid onset, duration of 30 to 40 minutes, and lack of significant complications at the lower dose, fentanyl has become an ideal choice for rapid, short-term analgesia in the emergency department. Recently, an extensive review of fentanyl use in the ED reported the safety and efficacy of this form of analgesia in this setting) There were few complications, and most occurred in the alcohol-intoxicated patient. A lively correspondence ensued. ,~ With this controversy in mind, we report a case of prolonged sedation, analgesia, and muscular relaxation in a multiple trauma patient caused by a continuous fentanyl infusion.
CASE REPORT
Mark Walsh, MD, FACEP* Greg A Smith, MDt Robert A Yount, MD, PhD¢ Frederick J Ferlic, MDt Martin F Wieschhaus, MD§ South Bend, Indiana From the Departments of Emergency Medicine,* Anesthesiology,t Surgery,$ and Family Practice,§ Saint Joseph's Medical Center, South Bend, Indiana. Received for publication October 22, 1990. Revision received January 25, 1991. Accepted for publication February 18, 1991. Address for reprints: Mark Walsh, MD, FACER Department of Emergency Medicine, Saint Joseph's Medical Center, 801 East LaSalle Street, South Bend, Indiana 46617.
A 50-kg, 21-year-old woman sustained bilateral midshaft femoral fractures in a motor vehicle accident. After a brief period of stabilization in the ED, the patient was taken to the radiology department for computed tomography (CT) scan of the head and abdomen. During the studies, she became combative and screamed loudly while thrashing about. Her vital signs and arterial blood gases were normal. A serum alcohol and subsequent drug screen were negative. The patient vomited, and 25 mg IV promethazine followed by 10 mg IV valium stopped the vomiting but failed to calm her. Meperidine 50 mg IV was then given without any sedation. At this point, 100 I~g fentanyl IV was infused in 50-t~g aliquots over two to three minutes with some sedation. Ten minutes later, an additional 100 t~g was given in a similar fashion to complete the CT. Approximately 30 minutes after the final dose of fentanyl, the patient again became combative. During the next two hours in the ED, she was given an additional 300 t~g fentanyl in 50-1~g boluses. She was intubated to protect the airway but soon was awake, moving her extremities, pulling out her IV lines, and requiring restraints. After intubation and hyperventilation, it was hoped that she could be sedated with IV morphine. However, there was no response to a 14-rag IV bolus of morphine. Despite negative head CT, we believed that the patient probably had a cerebral contusion of the temporal lobe. (In fact, 48 hours later, a CT head scan demonstrated both frontal and temporal lobe contusions.) We wanted to stabilize the patient before surgery and contemplated paralyzing her. We could not guarantee predictable and adequate sedation for this patient because of her manifest tolerance to meperidine, morphine, and diazepam. Neuromuscular blockade without controlled and reliable sedation would subject her to unnecessary physiologic and psychologic stress, which we wanted to avoid because of our suspicion, later confirmed, that she had a cerebral contusion. Because fentanyl is 150 times more potent than mor-
132/913
Annals of Emergency Medicine
20:8 August 1991
FENTANYL Walsh et a{
phine, l we knew that the 14-rag bolus of morphine corresponded to only a fraction of the total dose of fentanyl that had been required to sedate her. Rather than search for a new effective bolus dose of morphine to sedate the patient and then use a c o n t i n u o u s m o r p h i n e infusion to maintain sedation, we decided to use the medication that had proven effective in the preceding hours and follow with a continuous fentanyl infusion. Therefore, after consultation with an anesthesiologist, we elected to use a continuous fentanyl infusion for sedation, muscle relaxation, and analgesia. The patient was given a 100-b~g fentanyl bolus followed by a continuous fentanyl infusion. This infusion was prepared by diluting 50 mL (50 p.g/mL} of fentanyl in 500 mL of 5% dextrose in water to give a concentration of 5 ~,g/mL. Sedation and light anesthesia that allowed for eye opening when her name was called were achieved at a rate of 5.0 ~tg/min (0.1 p.g/kg/min). The patient was transferred to the ICU, and over the next eight hours the fentanyl infusion was gradually discontinued. The patient's fractures were subsequently repaired. She made an uneventful recovery. DISCUSSION Fentanyl is always given as a bolus for analgesia in the ED. Outpatient use of constant infusion fentanyl has been described for elective gynecologic surgery, such as dilatation and extraction procedures in the operating room setting. 4 However, prolonged fentanyl infusion in the ED for analgesia, sedation, or muscle relaxation has not been described. We elected to use fentanyl in lieu of a neuromuscular blocking agent combined with a narcotic because of our desire to avoid the hypotension associated with morphine, the patient's relative tolerance to diazepam, and our prior success in sedating her with fentanyl. We found an easily titratable, immediately reversible, and safe agent that gives excellent sedation, analgesia, and muscle relaxation in the ED. In situations in which there is manifest tolerance to benzodiazepenes or neuromuscular blocking agents are contraindicated, fentanyl represents an alternative to the combination of neuromuscular blocking agents and diazepam or morphine, which is most often used 20:8 August 1991
to control these types of patients. Its use in this setting also allows for imm e d i a t e reversal and s u b s e q u e n t neurologic evaluation by a neurosurgeon. As with all narcotic analgesics, complications can follow the use of fentanyl. Although respiratory depression and vomiting are uncommon with a low dose, our patient was intubated to protect her airway given her cerebral contusions and unstable condition. Even without these indications, intubation is necessary for a patient treated with a fentanyl infusion. Thoracic wall rigidity and glottic closure have been reported during the induction of anesthesia with high doses of fentanyl. -~ These complications are easily reversed w i t h naloxone. At the l o w - b o l u s doses, muscular rigidity and glottic closure are unlikely), 6 However, delayed rigidity occurs in anesthetic doses four to six hours after surgery due to re-entry of fentanyl from adipose tissue, muscle, and the gastrointestinal tract.6, 7 Therefore, prolonged low-dose adm i n i s t r a t i o n could t h e o r e t i c a l l y cause fentanyl's accumulation with delayed respiratory depression. Other adverse drug reactions such as hypertension, bradycardia, s and generalized seizures have been reported with high doses of fentanyl, although the association between seizures and fentanyl is not conclusive. 2 We were able to maintain sedation, analgesia, and muscle relaxation at a starting dose of 5 btg/min (0.1 ~g/kg/ rain} after the initial bolus of fentanyl. This dose is at the low end of the spectrum for outpatient anesthesia in the operating suite, where anesthesia was r e p o r t e d l y obtained with a fentanyl infusion of 2 to 50 p.g/min following a 100-btg fentanyl bolus5 Although the early prior doses of meperidine, diazepam, and, subsequently, morphine may have added to the sedative and analgesic effects of fentanyl, the total dose of fentanyl was much greater in potency compared with the doses of meperidine and morphine. Simply put, fentanyl provided the bulk of the sedation. Also, during most of the fentanyl infusion, the effects of the other medications had probably dissipated. We c o u l d have e l e c t e d to use higher doses of morphine until sedation, following with continuous morAnnals of Emergency Medicine
phine infusion. However, morphine, because of a low lipid solubility, has a ten- to 15-minute lag-to-peak effect. Fentanyl is more lipid soluble and therefore acts within one to two minutes when given IV.9 The choice of f e n t a n y l bolus and i n f u s i o n over morphine bolus and infusion was b a s e d n o t o n l y on t h i s p h a r macokinetic difference but also on our desire to avoid h y p o t e n s i o n , which occurs rarely with fentanyl but frequently with even small doses of morphine, s,m and on our earlier success in sedating our patient with frequent boluses of the more rapidacting fentanyl. Our decision to use a fentanyl infusion instead of a neuromuscular blocking agent combined with a narcotic or a benzodiazepene was based on our concern for the well-documented and detrimental physiologic stress of neuromuscular blockade in the absence of guaranteed sedation. Recently, in traumatic brain injury, c o n t i n u o u s m o r p h i n e infusion reduced the main baseline EEG activity and decreased patient stimulation more than bolus morphine during endotracheal suction of intubated patients. ~ For the reasons mentioned above, we elected to use fentanyl instead of morphine. SUMMARY
Fentanyl is an attractive agent for analgesia, muscle relaxation, and sedation in the ED. There is ample documentation in the literature confirming its safety and efficacy in this setting. We found that a fentanyl bolus followed by an infusion gave rapid, predictable, titratable, and reversible muscle relaxation, analgesia, and sedation of a combative patient who had marked tolerance to other narcotic analgesics and benzodiazepenes. Such a use of fentanyl may provide an alternative to the combined use of neuromuscular blocking agents and narcotics or benzodiazepenes for patients with significant tolerance to benzodiazepenes or for patients in w h o m n e u r o m u s c u l a r agents are contraindicated. The authors thank Pat Sobchak for her preparation of the manuscript and Elaine Flemming, BSN, for her assistance in the care of this patient. REFERENCES 1. Billmire DA, Neale HW, Gregory RO: Use of IV fen tanyl in the outpatient treatment of pediatric facial trauma. / "Fraum~l 1985;25:[079-1080.
914/133
FENTANYL Walsh et al
2. Chudnofsky CR, Wright SW, Dronen SW, et al: The safety of fentanyl use in the emergency department. Am7 Emcrg Med 1989;L8:635,2639. 3 Dronen SC, Wright SW, Chudnofsky CR: Anes thctics in the ED iletter). Ann EmerR Med 1991]; 19:839-840. 4 White PF: Use of continuous infusion versus inter mittent bolus administration of fentanyl or ketamine during outpatient anesthesia. Anesthesi¢dr~Ry 198~; 59:294 300. 5. Arandia HY, Patil VU: Glottic closure folh~wiil~
134/915
large dose of fentanyl (letter[. Anesthesi(dcJ~y 1987;66: 574 575 6. Caspi J, Klausner IM, Safadi T, ct al: Delayed respiratory depression fl~llowing fentallyl anesthesia h}r car diac surgery. Crit Care Med 1988;16:238 240. 7. Klausner IM, Caspi ], Lelcuk S, et al: I)clayed mus cular rigidity and respiratory depression following fcntanyl anesthesia. Arch Surx 1988;123:66-67 8 Bailey PL, Stanley TH: l'harmacology of intravenous narcotic anesthetics, in Miller RD led): Ane.~lhv.~ia. cd New York, Chtlrchill Livingstone, 1986, wll I, p
Annals of Emergency Medicine
754-759
9. C~ok LD: Opioids, in l)ripps RD, Eckenhotf JE, Van ~ dam LI) Ceds}: Intrlldu~ii~Jll to Anesthesia. cd 7 Phila de]phia, WB Satmders, 1988, p 162 10 R~Jscow CE, Moss J, Philbin I)M, et al: Histamine release during morphine and fentany/ anesthesia , 4 n v ; th;~ioh)~y 1982;56:93 11. Walsh 1C, Hoyt DB, Shackford SR, et al: A comparison ot N}lus vemus COiltinuotts opiate administration ill head injury: Effects of the processed EEG and intra crania/ pressure [ahstractl "haum~ 1990;30:930
20:8 August 1991
Continuous Intravenous Infusion Fentanyl for Sedation and Analgesia of the Multiple Trauma Patient Fentanyl is an attractive agent for analgesia in the emergency department. Its use in this setting has been limited to IV bolus administration. We report successful sedation, muscle relaxation, and analgesia of a multiple trauma patient with fentanyl IV bolus and continuous infusion in the ED. [Walsh M, Smith GA, Yount RA, Ferlic FJ, Wieschhaus MF: Continuous intravenous infusion fentanyl for sedation and analgesia of the multiple trauma patient. Ann Emerg Med August 1991;20:913-915.] INTRODUCTION Fentanyl is a synthetic narcotic analgesic that has a potency 150 times that of morphine.l Because of its rapid onset, duration of 30 to 40 minutes, and lack of significant complications at the lower dose, fentanyl has become an ideal choice for rapid, short-term analgesia in the emergency department. Recently, an extensive review of fentanyl use in the ED reported the safety and efficacy of this form of analgesia in this setting) There were few complications, and most occurred in the alcohol-intoxicated patient. A lively correspondence ensued. ,~ With this controversy in mind, we report a case of prolonged sedation, analgesia, and muscular relaxation in a multiple trauma patient caused by a continuous fentanyl infusion.
CASE REPORT
Mark Walsh, MD, FACEP* Greg A Smith, MDt Robert A Yount, MD, PhD¢ Frederick J Ferlic, MDt Martin F Wieschhaus, MD§ South Bend, Indiana From the Departments of Emergency Medicine,* Anesthesiology,t Surgery,$ and Family Practice,§ Saint Joseph's Medical Center, South Bend, Indiana. Received for publication October 22, 1990. Revision received January 25, 1991. Accepted for publication February 18, 1991. Address for reprints: Mark Walsh, MD, FACER Department of Emergency Medicine, Saint Joseph's Medical Center, 801 East LaSalle Street, South Bend, Indiana 46617.
A 50-kg, 21-year-old woman sustained bilateral midshaft femoral fractures in a motor vehicle accident. After a brief period of stabilization in the ED, the patient was taken to the radiology department for computed tomography (CT) scan of the head and abdomen. During the studies, she became combative and screamed loudly while thrashing about. Her vital signs and arterial blood gases were normal. A serum alcohol and subsequent drug screen were negative. The patient vomited, and 25 mg IV promethazine followed by 10 mg IV valium stopped the vomiting but failed to calm her. Meperidine 50 mg IV was then given without any sedation. At this point, 100 I~g fentanyl IV was infused in 50-t~g aliquots over two to three minutes with some sedation. Ten minutes later, an additional 100 t~g was given in a similar fashion to complete the CT. Approximately 30 minutes after the final dose of fentanyl, the patient again became combative. During the next two hours in the ED, she was given an additional 300 t~g fentanyl in 50-1~g boluses. She was intubated to protect the airway but soon was awake, moving her extremities, pulling out her IV lines, and requiring restraints. After intubation and hyperventilation, it was hoped that she could be sedated with IV morphine. However, there was no response to a 14-rag IV bolus of morphine. Despite negative head CT, we believed that the patient probably had a cerebral contusion of the temporal lobe. (In fact, 48 hours later, a CT head scan demonstrated both frontal and temporal lobe contusions.) We wanted to stabilize the patient before surgery and contemplated paralyzing her. We could not guarantee predictable and adequate sedation for this patient because of her manifest tolerance to meperidine, morphine, and diazepam. Neuromuscular blockade without controlled and reliable sedation would subject her to unnecessary physiologic and psychologic stress, which we wanted to avoid because of our suspicion, later confirmed, that she had a cerebral contusion. Because fentanyl is 150 times more potent than mor-
132/913
Annals of Emergency Medicine
20:8 August 1991
FENTANYL Walsh et a{
phine, l we knew that the 14-rag bolus of morphine corresponded to only a fraction of the total dose of fentanyl that had been required to sedate her. Rather than search for a new effective bolus dose of morphine to sedate the patient and then use a c o n t i n u o u s m o r p h i n e infusion to maintain sedation, we decided to use the medication that had proven effective in the preceding hours and follow with a continuous fentanyl infusion. Therefore, after consultation with an anesthesiologist, we elected to use a continuous fentanyl infusion for sedation, muscle relaxation, and analgesia. The patient was given a 100-b~g fentanyl bolus followed by a continuous fentanyl infusion. This infusion was prepared by diluting 50 mL (50 p.g/mL} of fentanyl in 500 mL of 5% dextrose in water to give a concentration of 5 ~,g/mL. Sedation and light anesthesia that allowed for eye opening when her name was called were achieved at a rate of 5.0 ~tg/min (0.1 p.g/kg/min). The patient was transferred to the ICU, and over the next eight hours the fentanyl infusion was gradually discontinued. The patient's fractures were subsequently repaired. She made an uneventful recovery. DISCUSSION Fentanyl is always given as a bolus for analgesia in the ED. Outpatient use of constant infusion fentanyl has been described for elective gynecologic surgery, such as dilatation and extraction procedures in the operating room setting. 4 However, prolonged fentanyl infusion in the ED for analgesia, sedation, or muscle relaxation has not been described. We elected to use fentanyl in lieu of a neuromuscular blocking agent combined with a narcotic because of our desire to avoid the hypotension associated with morphine, the patient's relative tolerance to diazepam, and our prior success in sedating her with fentanyl. We found an easily titratable, immediately reversible, and safe agent that gives excellent sedation, analgesia, and muscle relaxation in the ED. In situations in which there is manifest tolerance to benzodiazepenes or neuromuscular blocking agents are contraindicated, fentanyl represents an alternative to the combination of neuromuscular blocking agents and diazepam or morphine, which is most often used 20:8 August 1991
to control these types of patients. Its use in this setting also allows for imm e d i a t e reversal and s u b s e q u e n t neurologic evaluation by a neurosurgeon. As with all narcotic analgesics, complications can follow the use of fentanyl. Although respiratory depression and vomiting are uncommon with a low dose, our patient was intubated to protect her airway given her cerebral contusions and unstable condition. Even without these indications, intubation is necessary for a patient treated with a fentanyl infusion. Thoracic wall rigidity and glottic closure have been reported during the induction of anesthesia with high doses of fentanyl. -~ These complications are easily reversed w i t h naloxone. At the l o w - b o l u s doses, muscular rigidity and glottic closure are unlikely), 6 However, delayed rigidity occurs in anesthetic doses four to six hours after surgery due to re-entry of fentanyl from adipose tissue, muscle, and the gastrointestinal tract.6, 7 Therefore, prolonged low-dose adm i n i s t r a t i o n could t h e o r e t i c a l l y cause fentanyl's accumulation with delayed respiratory depression. Other adverse drug reactions such as hypertension, bradycardia, s and generalized seizures have been reported with high doses of fentanyl, although the association between seizures and fentanyl is not conclusive. 2 We were able to maintain sedation, analgesia, and muscle relaxation at a starting dose of 5 btg/min (0.1 ~g/kg/ rain} after the initial bolus of fentanyl. This dose is at the low end of the spectrum for outpatient anesthesia in the operating suite, where anesthesia was r e p o r t e d l y obtained with a fentanyl infusion of 2 to 50 p.g/min following a 100-btg fentanyl bolus5 Although the early prior doses of meperidine, diazepam, and, subsequently, morphine may have added to the sedative and analgesic effects of fentanyl, the total dose of fentanyl was much greater in potency compared with the doses of meperidine and morphine. Simply put, fentanyl provided the bulk of the sedation. Also, during most of the fentanyl infusion, the effects of the other medications had probably dissipated. We c o u l d have e l e c t e d to use higher doses of morphine until sedation, following with continuous morAnnals of Emergency Medicine
phine infusion. However, morphine, because of a low lipid solubility, has a ten- to 15-minute lag-to-peak effect. Fentanyl is more lipid soluble and therefore acts within one to two minutes when given IV.9 The choice of f e n t a n y l bolus and i n f u s i o n over morphine bolus and infusion was b a s e d n o t o n l y on t h i s p h a r macokinetic difference but also on our desire to avoid h y p o t e n s i o n , which occurs rarely with fentanyl but frequently with even small doses of morphine, s,m and on our earlier success in sedating our patient with frequent boluses of the more rapidacting fentanyl. Our decision to use a fentanyl infusion instead of a neuromuscular blocking agent combined with a narcotic or a benzodiazepene was based on our concern for the well-documented and detrimental physiologic stress of neuromuscular blockade in the absence of guaranteed sedation. Recently, in traumatic brain injury, c o n t i n u o u s m o r p h i n e infusion reduced the main baseline EEG activity and decreased patient stimulation more than bolus morphine during endotracheal suction of intubated patients. ~ For the reasons mentioned above, we elected to use fentanyl instead of morphine. SUMMARY
Fentanyl is an attractive agent for analgesia, muscle relaxation, and sedation in the ED. There is ample documentation in the literature confirming its safety and efficacy in this setting. We found that a fentanyl bolus followed by an infusion gave rapid, predictable, titratable, and reversible muscle relaxation, analgesia, and sedation of a combative patient who had marked tolerance to other narcotic analgesics and benzodiazepenes. Such a use of fentanyl may provide an alternative to the combined use of neuromuscular blocking agents and narcotics or benzodiazepenes for patients with significant tolerance to benzodiazepenes or for patients in w h o m n e u r o m u s c u l a r agents are contraindicated. The authors thank Pat Sobchak for her preparation of the manuscript and Elaine Flemming, BSN, for her assistance in the care of this patient. REFERENCES 1. Billmire DA, Neale HW, Gregory RO: Use of IV fen tanyl in the outpatient treatment of pediatric facial trauma. / "Fraum~l 1985;25:[079-1080.
914/133
FENTANYL Walsh et al
2. Chudnofsky CR, Wright SW, Dronen SW, et al: The safety of fentanyl use in the emergency department. Am7 Emcrg Med 1989;L8:635,2639. 3 Dronen SC, Wright SW, Chudnofsky CR: Anes thctics in the ED iletter). Ann EmerR Med 1991]; 19:839-840. 4 White PF: Use of continuous infusion versus inter mittent bolus administration of fentanyl or ketamine during outpatient anesthesia. Anesthesi¢dr~Ry 198~; 59:294 300. 5. Arandia HY, Patil VU: Glottic closure folh~wiil~
134/915
large dose of fentanyl (letter[. Anesthesi(dcJ~y 1987;66: 574 575 6. Caspi J, Klausner IM, Safadi T, ct al: Delayed respiratory depression fl~llowing fentallyl anesthesia h}r car diac surgery. Crit Care Med 1988;16:238 240. 7. Klausner IM, Caspi ], Lelcuk S, et al: I)clayed mus cular rigidity and respiratory depression following fcntanyl anesthesia. Arch Surx 1988;123:66-67 8 Bailey PL, Stanley TH: l'harmacology of intravenous narcotic anesthetics, in Miller RD led): Ane.~lhv.~ia. cd New York, Chtlrchill Livingstone, 1986, wll I, p
Annals of Emergency Medicine
754-759
9. C~ok LD: Opioids, in l)ripps RD, Eckenhotf JE, Van ~ dam LI) Ceds}: Intrlldu~ii~Jll to Anesthesia. cd 7 Phila de]phia, WB Satmders, 1988, p 162 10 R~Jscow CE, Moss J, Philbin I)M, et al: Histamine release during morphine and fentany/ anesthesia , 4 n v ; th;~ioh)~y 1982;56:93 11. Walsh 1C, Hoyt DB, Shackford SR, et al: A comparison ot N}lus vemus COiltinuotts opiate administration ill head injury: Effects of the processed EEG and intra crania/ pressure [ahstractl "haum~ 1990;30:930
20:8 August 1991
