Benzodiazepinesfor Acute Pain in Children
Chlldrtn with complaints of severe pain require a comprehensive and vkmatic approach to suuxssfblly asacu~and treat their pain. Opioid analgesics, generally the mainstay of pharmac&gic pain management in the hospital setting, appear to have a limited tiect on pain co~plairkts in some clinical siituations. When pain is rekxctory and unre sponsivtto appropriate use of analgesic agents, there might be additional dirnensiona of the pain that arc not addressed by the aulgesic~, Our pediatric muMiscipEwry pain teami has found hetiiazepines to be
useful adjunctbe phiu3nacologic agents in the treatment of dclcetcd acute pain cornpItints that are refractory to analguk agents In the fbUowing illustrarhe caacs, we diacuaa pediatric clinicalsituations in which benzod&
=pinm have been effective in alleviating severe pain complaints while decreasing opi&l requirements.
cqing,
zutd complaining of srxrc pain. Her c&givcra were uuable to engage her in convcr~lion ahout her anxieties due to the scvtiqofherpain complaints. The surgeous could find no organic expknation for the severity of her distress. Because tKa child demonstratedhehavioraconsistent with zmxiety not nw related to pain and because her diim seemed to he increzuing when post~~ve pain should be decree ing, one member of the p&n team suggested that this child be given 0.25 mg of IV Ioraacpam as well as change her opioid order. There was a delay in administmtionof the newly ordered apMd and the child received the ‘orazepam S hr following her last morphine dose. within 90 min and before any further opioid auaIgc& was given the child rqxwtcd dramatic reduction in her pain, At this time she was able to talk ahut her anxieties regarding her condition and surgery. She was able to dii her fear of dying and he fact that one of her cbmates had died tie week prior to her surgery. After the initiai dose of lorazepam, the &W’s pain, which previously had been severe and refractory, became very well controlled on a small dose of buprenorphiue IV every 8 hr alternating with the 0.25 mg ofIVlomzepam. Her subsequent pain ratings con&tently remained helow 5 on a llI&oint xale.
lO-point scale) whenem hiskgwal8mauipllhued. Several @aid =u+@& reghuex~ i.ucWing morphine trh pa&nt+Bnlrouecl aua@ia had Wed to umtrol his pain. J3ecausemuchoftid&tr~wasb&vcdw beduet&ara&nticipationofp&tt,it~ recommended tbat he receive 2.5 mg of IV &azepam.Tllisrch%edhimtothepomt whereheandapainGcarrrmemhcrcould di!xusshiianxieticsaadncgodaKe~c.are WiththCSurgeaar.HC~tbc~
for him su&quent m that he tolerated e%uemelywellwitbminimal pain complain&
opioias
&se4
An lly~ld girl with severe swc c.em bral p&y and mental retardation was operated on for hamsrring release. One day following surgery the child appeared agitated, grimacing and crying&spite receiving IVm0rpbineO.lmg/kgevay2hr.Dia2epam (2 mg by mouth) was added to her medications and within 1 hr the child’s pain behaviors disappeared. The child recovered un~tfullywitb gradual taperingclfnarcot* its and s&sequent discontinuation of the lowdose diaSpam witbout any further bthavi4xal signs ofdistNl3. cbse3 A 17-yrsld adolexcnt
with a bone tumor was receiving repeat dcbridements fM a skin fIap. He complained of severe pain (10 on a
An 18-yMld XMeSceut who -ted with SicklMCIl p&l crisis complained 3cvcrepaill@cKlaBSpoirltaG3k).#cr severaIhollrShehadrcc~twodOKSof75 mgmeperidincwith25nlgb+oz+ncJM a8wellasCMledoreaf8mgrvmwphinewi~
of
494
Ridztsmeieret al.
minimal pain relief. The patient was then given 2 mg levorphanol intravenously, but his pain persisted. Subsequently, 0.25 mg by mouth alprazolam was added to the regimen and within 1 hr the patient stated, “now my muscles feel relaxed.” He reported dramatic improvement in pain, slept moderately well, and was discharged from the hospital on oral analgesics alone within 16 hr of receiving the alprazolam. Di&ussion During acute painful episodes, concurrent anxiety and insomnia are frequently encountered in pediatric patients. In addition, muscle spasms contribute to the distress complaints of selected pediatric orthopedic postoperative patients. Although fear and anxiety almost uniformly accompany severe pain, the use of benzodiazepines has been discouraged in recent reviews and recommendations regarding management of pain in children.*p3 Likewise, benzodiazepines are considered overemphasized and overu~d for the treatment of pain associated with muscle spasm.*s4 Benzodiazepines have anxiolytic, sedative, muscle relaxant, hypnotic, anticonvulsant, and amnestic effects.5 They are useful agents as premeditations for surgery and procedures.* Fernandez and colleagues6 reported alprazolam to be a useful adjunct to opioids when treating deafferentation-causalgic type of pain but not useful for somatic pain. We have found benzodiazepines to be extremely useful agents in reducing the distress associated with severe pain complaints in selected pediatric patients. We do not advocate their use in such situations without appropriate analgesics. In addition, we do not suggest that benzodiazepines are indicated for all anxious patients with pain or that they be used as replacement therapy for dealing directly with a child’s anxiety. Anxieties should be addressed by individuals with sufficient time, sensitivity, and expertise. As illustrated in the cases above, however, even single administration of low-dose benzodiazepines can help bring a highly distressed child to a state in which associated problems can be more effectively addressed. Although benzodiazepines do not seem
Vol. 7No. 8 AIovenuier1992
needed in the pain management of most postoperative orthopedic patients, these agents can be extremely effective adjuncts in the pain management of postoperative pediatric orthopedic patients whose pain is relatively unresponsive to conventional doses of analgesics, in our experience especially those patients with spastic cerebral palsy. After some procedures, such as osteotomies and tendon releases, localized muscle spasm appears to contribute to the discomfort. The addition of nonpharmacologic therapies such as massage and/or the addition of a benzodiazepine when used in conjunction with analgesics can reduce muscle spasm and thus improve the patients’ comfort. It is conceivabie that at least a portion of the favorable response to benzodiazepines we observe in some children with vasoocclusive crisis is due to its effect as a muscle relaxant. Controlled clinical trials evaluating the efficacy of low-dose benzodiazepines in specific populations would add greatly to our understanding of indications for benzodiazepines and their reasons for efficacy in such situations. Most of the actions of benzodiazepines appear to result from potentiation of the chief central nervous system inhibitory neurotransmitter, y aminobutyric acid. Benzodiazepines as a group are noted for their high therapeutic-toxic ratio.7 Caution is required, however, when using them as adjuvants in pain management. Their sedative and respiratory depressant effects are increased by combined use with opioids and adverse effects are dependent on dose, route, and rate of administration, age, and the clinical situation.* Intravenous use of a short-acting benzodiazepine, such as midazolam, in combination with opioids poses a significant risk of respiratory depression. This is one reason why we have not used intravenous midazolam as an adjuvant for acute pain management on the general pediatric unit. When high doses of benzodiazepines and opioids are used in conjunction, this should likewise be done in controlled environments with cardiorespiratory monitoring. We have not found clinically significant respiratory depression when using low-dose, intermediate, or longacting benzodiazepines in conjunction with opioid analgesic equivalent doses up to 0.1
vol.7 No. 8 Nov~Ei- I992
plswe to an
istration.
to short-term
use.
chtsmeier AJ, Alexander Maikler V. A descrip aged by an interdi~i~l~n~ pediatric pain eeam: Second international symposium on Montreal, Canada, 4/26/91. J Pain
issues. Unfortunately,
there are no
measures all can overla must ascertain the most effective therapy for the distress that accompanies painful episodes. Initially clinicians must ensure that inadequately managed pain is not due to inappropriate use of analgesic agents, sue itw,ufficient dose or intervals that are
too far apart. Problems with delivery systems can also occur and should be assessed. Pain management is guided by assessment that considers the pain complaints in relation to the individual child and the clinical context. If analgesics alone are used to address all distress associated with pain, they must be used in unnecesstily high doses leading to undesirable side effects. In some clinical situations, the addition of a benzodiazepine can reduce the amount of opioid and other analgesics required and therefore can be “opioid sparing.” In the highly distressed
2. Schecheer N, Altman A, We&man S, et al. Report of the consensus conference on the management of pain in childhood cancer. Pediatrics 1990;86MS=834. 3. Shapiro BS. The management of pain in sickle cell disease. Pediatr Clin North Am 1989$X%1028-1045. 4. Shannan M, Berde CB. Pharmacological management of pain in children and adolescents. Pediatr Clin North Am 198686~855-87B. 1 TW, Nies AS, Taylor P. 5. Goodman GA, Goodman and Giian’s: the pharmacological basic of therapeutics. Elmsford, NYzPergamon, 1990. 6. Fernandez F, Adams F, Holmes VF, Analgesic effect of alprazolam in patients with chronic, organic pain of malignant origin. J Clin Psychopharmacol 1987;7:167-169. 7. Gaudreauh P, Guay J, Thivierge RL, Verdy I[. Benzodiazepine poisoning: clinical and pharmacological considerations and treatment. Drug Safety 1991;&.247-265. 8. Yaseer M, Nichols DG, DeshpandeJK, Wetzel RC. Midazolam-fentanyl intravenous sedation in children: case report of respiratory arrest. Pediatrics 1990;86:46.3-467.
Chlldrtn with complaints of severe pain require a comprehensive and vkmatic approach to suuxssfblly asacu~and treat their pain. Opioid analgesics, generally the mainstay of pharmac&gic pain management in the hospital setting, appear to have a limited tiect on pain co~plairkts in some clinical siituations. When pain is rekxctory and unre sponsivtto appropriate use of analgesic agents, there might be additional dirnensiona of the pain that arc not addressed by the aulgesic~, Our pediatric muMiscipEwry pain teami has found hetiiazepines to be
useful adjunctbe phiu3nacologic agents in the treatment of dclcetcd acute pain cornpItints that are refractory to analguk agents In the fbUowing illustrarhe caacs, we diacuaa pediatric clinicalsituations in which benzod&
=pinm have been effective in alleviating severe pain complaints while decreasing opi&l requirements.
cqing,
zutd complaining of srxrc pain. Her c&givcra were uuable to engage her in convcr~lion ahout her anxieties due to the scvtiqofherpain complaints. The surgeous could find no organic expknation for the severity of her distress. Because tKa child demonstratedhehavioraconsistent with zmxiety not nw related to pain and because her diim seemed to he increzuing when post~~ve pain should be decree ing, one member of the p&n team suggested that this child be given 0.25 mg of IV Ioraacpam as well as change her opioid order. There was a delay in administmtionof the newly ordered apMd and the child received the ‘orazepam S hr following her last morphine dose. within 90 min and before any further opioid auaIgc& was given the child rqxwtcd dramatic reduction in her pain, At this time she was able to talk ahut her anxieties regarding her condition and surgery. She was able to dii her fear of dying and he fact that one of her cbmates had died tie week prior to her surgery. After the initiai dose of lorazepam, the &W’s pain, which previously had been severe and refractory, became very well controlled on a small dose of buprenorphiue IV every 8 hr alternating with the 0.25 mg ofIVlomzepam. Her subsequent pain ratings con&tently remained helow 5 on a llI&oint xale.
lO-point scale) whenem hiskgwal8mauipllhued. Several @aid =u+@& reghuex~ i.ucWing morphine trh pa&nt+Bnlrouecl aua@ia had Wed to umtrol his pain. J3ecausemuchoftid&tr~wasb&vcdw beduet&ara&nticipationofp&tt,it~ recommended tbat he receive 2.5 mg of IV &azepam.Tllisrch%edhimtothepomt whereheandapainGcarrrmemhcrcould di!xusshiianxieticsaadncgodaKe~c.are WiththCSurgeaar.HC~tbc~
for him su&quent m that he tolerated e%uemelywellwitbminimal pain complain&
opioias
&se4
An lly~ld girl with severe swc c.em bral p&y and mental retardation was operated on for hamsrring release. One day following surgery the child appeared agitated, grimacing and crying&spite receiving IVm0rpbineO.lmg/kgevay2hr.Dia2epam (2 mg by mouth) was added to her medications and within 1 hr the child’s pain behaviors disappeared. The child recovered un~tfullywitb gradual taperingclfnarcot* its and s&sequent discontinuation of the lowdose diaSpam witbout any further bthavi4xal signs ofdistNl3. cbse3 A 17-yrsld adolexcnt
with a bone tumor was receiving repeat dcbridements fM a skin fIap. He complained of severe pain (10 on a
An 18-yMld XMeSceut who -ted with SicklMCIl p&l crisis complained 3cvcrepaill@cKlaBSpoirltaG3k).#cr severaIhollrShehadrcc~twodOKSof75 mgmeperidincwith25nlgb+oz+ncJM a8wellasCMledoreaf8mgrvmwphinewi~
of
494
Ridztsmeieret al.
minimal pain relief. The patient was then given 2 mg levorphanol intravenously, but his pain persisted. Subsequently, 0.25 mg by mouth alprazolam was added to the regimen and within 1 hr the patient stated, “now my muscles feel relaxed.” He reported dramatic improvement in pain, slept moderately well, and was discharged from the hospital on oral analgesics alone within 16 hr of receiving the alprazolam. Di&ussion During acute painful episodes, concurrent anxiety and insomnia are frequently encountered in pediatric patients. In addition, muscle spasms contribute to the distress complaints of selected pediatric orthopedic postoperative patients. Although fear and anxiety almost uniformly accompany severe pain, the use of benzodiazepines has been discouraged in recent reviews and recommendations regarding management of pain in children.*p3 Likewise, benzodiazepines are considered overemphasized and overu~d for the treatment of pain associated with muscle spasm.*s4 Benzodiazepines have anxiolytic, sedative, muscle relaxant, hypnotic, anticonvulsant, and amnestic effects.5 They are useful agents as premeditations for surgery and procedures.* Fernandez and colleagues6 reported alprazolam to be a useful adjunct to opioids when treating deafferentation-causalgic type of pain but not useful for somatic pain. We have found benzodiazepines to be extremely useful agents in reducing the distress associated with severe pain complaints in selected pediatric patients. We do not advocate their use in such situations without appropriate analgesics. In addition, we do not suggest that benzodiazepines are indicated for all anxious patients with pain or that they be used as replacement therapy for dealing directly with a child’s anxiety. Anxieties should be addressed by individuals with sufficient time, sensitivity, and expertise. As illustrated in the cases above, however, even single administration of low-dose benzodiazepines can help bring a highly distressed child to a state in which associated problems can be more effectively addressed. Although benzodiazepines do not seem
Vol. 7No. 8 AIovenuier1992
needed in the pain management of most postoperative orthopedic patients, these agents can be extremely effective adjuncts in the pain management of postoperative pediatric orthopedic patients whose pain is relatively unresponsive to conventional doses of analgesics, in our experience especially those patients with spastic cerebral palsy. After some procedures, such as osteotomies and tendon releases, localized muscle spasm appears to contribute to the discomfort. The addition of nonpharmacologic therapies such as massage and/or the addition of a benzodiazepine when used in conjunction with analgesics can reduce muscle spasm and thus improve the patients’ comfort. It is conceivabie that at least a portion of the favorable response to benzodiazepines we observe in some children with vasoocclusive crisis is due to its effect as a muscle relaxant. Controlled clinical trials evaluating the efficacy of low-dose benzodiazepines in specific populations would add greatly to our understanding of indications for benzodiazepines and their reasons for efficacy in such situations. Most of the actions of benzodiazepines appear to result from potentiation of the chief central nervous system inhibitory neurotransmitter, y aminobutyric acid. Benzodiazepines as a group are noted for their high therapeutic-toxic ratio.7 Caution is required, however, when using them as adjuvants in pain management. Their sedative and respiratory depressant effects are increased by combined use with opioids and adverse effects are dependent on dose, route, and rate of administration, age, and the clinical situation.* Intravenous use of a short-acting benzodiazepine, such as midazolam, in combination with opioids poses a significant risk of respiratory depression. This is one reason why we have not used intravenous midazolam as an adjuvant for acute pain management on the general pediatric unit. When high doses of benzodiazepines and opioids are used in conjunction, this should likewise be done in controlled environments with cardiorespiratory monitoring. We have not found clinically significant respiratory depression when using low-dose, intermediate, or longacting benzodiazepines in conjunction with opioid analgesic equivalent doses up to 0.1
vol.7 No. 8 Nov~Ei- I992
plswe to an
istration.
to short-term
use.
chtsmeier AJ, Alexander Maikler V. A descrip aged by an interdi~i~l~n~ pediatric pain eeam: Second international symposium on Montreal, Canada, 4/26/91. J Pain
issues. Unfortunately,
there are no
measures all can overla must ascertain the most effective therapy for the distress that accompanies painful episodes. Initially clinicians must ensure that inadequately managed pain is not due to inappropriate use of analgesic agents, sue itw,ufficient dose or intervals that are
too far apart. Problems with delivery systems can also occur and should be assessed. Pain management is guided by assessment that considers the pain complaints in relation to the individual child and the clinical context. If analgesics alone are used to address all distress associated with pain, they must be used in unnecesstily high doses leading to undesirable side effects. In some clinical situations, the addition of a benzodiazepine can reduce the amount of opioid and other analgesics required and therefore can be “opioid sparing.” In the highly distressed
2. Schecheer N, Altman A, We&man S, et al. Report of the consensus conference on the management of pain in childhood cancer. Pediatrics 1990;86MS=834. 3. Shapiro BS. The management of pain in sickle cell disease. Pediatr Clin North Am 1989$X%1028-1045. 4. Shannan M, Berde CB. Pharmacological management of pain in children and adolescents. Pediatr Clin North Am 198686~855-87B. 1 TW, Nies AS, Taylor P. 5. Goodman GA, Goodman and Giian’s: the pharmacological basic of therapeutics. Elmsford, NYzPergamon, 1990. 6. Fernandez F, Adams F, Holmes VF, Analgesic effect of alprazolam in patients with chronic, organic pain of malignant origin. J Clin Psychopharmacol 1987;7:167-169. 7. Gaudreauh P, Guay J, Thivierge RL, Verdy I[. Benzodiazepine poisoning: clinical and pharmacological considerations and treatment. Drug Safety 1991;&.247-265. 8. Yaseer M, Nichols DG, DeshpandeJK, Wetzel RC. Midazolam-fentanyl intravenous sedation in children: case report of respiratory arrest. Pediatrics 1990;86:46.3-467.
