INTRODUCTION:
Opioids are used intrathecally to manage surgical pain. There are few reports of hypothermia after spinal morphine injection, none in the pediatric population. We present a teenager's case of mild hypothermia.

CASE PRESENTATION:
A 15-year-old boy was scheduled for elective abdominal laparotomy. General anesthesia was combined with spinal anesthesia, using levobupivacaine and morphine. In the recovery room, he presented a decreased tympanic temperature (34.4°C) associated with excessive sweating, hyperglycemia, and complained of feeling hot. All other vital signs were normal. It was decided to maintain clinical vigilance and hourly monitoring of temperature and glycaemia values. Despite active warming, he remained hypothermic for 16 hours, with gradual remission of symptoms and normalization of glycemic values. It is unknown how intrathecal morphine causes hypothermia. The most viable hypothesis is its effect on the hypothalamus. In our case the most probable causes of post anesthesia hypothermia were excluded; therefore, we can admit that the cause of hypothermia was the spinal administration of morphine. Some reports used naloxone and lorazepam successfully. In our report, they disappeared spontaneously 16 hours later, which corroborates our diagnosis.

CONCLUSIONS:
Children undergoing subarachnoid block with with intrathecal morphine may develop a disruption on thermoregulation, leading to a resistant postoperative hypothermia associated with excessive sweating.info:eu-repo/semantics/publishedVersio

Candeias, MJ

Caria, T

Cenicante, T

Da Silva, AV

Ferraz, S

English

Repository of the Hospital Center of Central Lisbon

Persistent Hypothermia and Excessive Sweating Following Intrathecal Morphine Administration in a Teenage Boy: A Case Report

Repositório do Centro Hospitalar de Lisboa Central, EPE

Anesth Pain Med. 2018 February; 8(1):e66724.Published online 2018 February 21.doi: 10.5812/aapm.66724.Case ReportPersistent Hypothermia and Excessive Sweating Following IntrathecalMorphine Administration in a Teenage Boy: A Case ReportSara Ferraz,1,* Telma Caria,2 Aline Vaz Da Silva,3 Maria Jose Candeias,4 and Teresa Cenicante41Anaesthesiology Department of Centro Hospitalar de Vila Nova de Gaia/Espinho, Vila Nova de Gaia, Portugal2Anaesthesiology Department of Centro Hospitalar Lisboa Ocidental, Lisboa, Portugal3Pediatric Surgery Department of Centro Hospitalar Lisboa Central, Hospital Dona Estefânia, Lisboa, Portugal4Anaesthesiology Department of Centro Hospitalar Lisboa Central, Hospital Dona Estefânia, Lisboa, Portugal*Corresponding author: Sara Ferraz, Anesthesiology trainee at Centro Hospitalar de Vila Nova de Gaia/Espinho, Rua Jose Joaquim Gomes da Silva, 59 - 6º Direito; 4460-171Matosinhos, Porto, Portugal. Tel: +35-1917468963, E-mail: sara.ferraz.lf@gmail.comReceived 2018 January 31; Accepted 2018 February 17.AbstractIntroduction: Opioids are used intrathecally to manage surgical pain. There are few reports of hypothermia after spinal morphine injection, none in the pediatricpopulation. We present a teenager’s case of mild hypothermia.Case Presentation: A 15-year-old boy was scheduled for elective abdominal laparotomy. General anesthesia was combined with spinal anesthesia, using levobupivacaineand morphine. In the recovery room, he presented a decreased tympanic temperature (34.4°C) associated with excessive sweating, hyperglycemia, and complained offeeling hot. All other vital signs were normal. It was decided to maintain clinical vigilance and hourly monitoring of temperature and glycaemia values. Despite activewarming, he remained hypothermic for 16 hours, with gradual remission of symptoms and normalization of glycemic values. It is unknown how intrathecal morphinecauses hypothermia. The most viable hypothesis is its effect on the hypothalamus. In our case the most probable causes of post anesthesia hypothermia were excluded;therefore, we can admit that the cause of hypothermia was the spinal administration of morphine. Some reports used naloxone and lorazepam successfully. In our report,they disappeared spontaneously 16 hours later, which corroborates our diagnosis.Conclusions: Children undergoing subarachnoid block with with intrathecal morphine may develop a disruption on thermoregulation, leading to a resistant postop-erative hypothermia associated with excessive sweating.Keywords: Anesthesia, Spinal, Pediatric Anesthesia, Hypothermia, Morphine1. IntroductionOpioids are often administered intrathecally to man-age intra and postoperative pain. Its popularity for pedi-atric patients has increased. It provides intense, safe, andprolonged postoperative analgesia (1).Intrathecal morphine has advantages as it decreasesthe need for postoperative opioids and it has a long dura-tion of action, by its administration at its site of real action -central nervous system, which is mediated by its action onthe opioid receptors in the spinal cord. Although there isa higher tolerance this way, adverse effects such as nauseaand vomiting, sedation, as well as respiratory depressionare still present (2). Hypothermia, described as a conse-quence of subarachnoid blockade, mainly by vasodilation,may be associated with morphine intrathecal administra-tion.There are few cases described, most of them in the ob-stetric population submitted to cesarean cession and 1 inan orthopedic patient (3). There is none in the pediatricpopulation.We present a case of hypothermia in a teenage boy afterintrathecal administration of morphine.2. Case PresentationA 15-year-old boy (body weight 49 kg, height 181 cm),ASA physical status II (allergic rhinitis, frequent epistaxis)was scheduled for elective surgery of a pelvic mass resec-tion. Besides anemia (9.3 g/dL) and an increased plateletcount (592× 109/L) his blood tests were normal.After premedication with oral midazolam, the boy wastaken to the operating room. Electrocardiogram, non-invasive blood pressure, pulse oximetry, and pediatric bis-pectral index sensor were used and his vitals were stable.After establishing peripheral intravenous (IV) access, 500mL of Ringer’s Lactate was started and an induction of in-travenous general anesthesia with fentanyl, propofol, androcuronium was performed following maintenance withsevoflurane.Next, a right radial artery line was placed followed byan ultrasound guided central venous catheter in the rightbrachiocephalic vein, without intercurrences.The teenage boy was then placed in a lateral decubitusposition and a subarachnoid block (SAB) was performedunder an ascetic technique with a 27 G quincke needle. Amedian approach was successfully performed after a sin-gle puncture at the L3 - L4 level. Correct placement of theCopyright © 2018, Anesthesiology and Pain Medicine. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided theoriginal work is properly cited.Ferraz S et al.needle was verified by a free flow of clear cerebrospinalfluid. Hyperbaric bupivacaine 0.5% (total 7.5 mg) plus mor-phine 0.200 mg (0.4 mcg/kg) were used for SAB.The child was positioned in dorsal decubitus, 1960 mgof cefazolin IV was administered and active warming wasstarted using a forced-air warming system.The patient’s vitals were stable during the wholesurgery, which lasted for 1 hour and 30 minutes and waseventless. His tympanic temperature (TT) was 35°C at theend of surgery.About 20 minutes after arriving at the recovery room,nearly 2 hours after the SAB, the boy presented a decreasedTT (34.4°C) associated with excessive sweating, no shiver-ing, hyperglycemia, nausea and complained of feeling hot.All other vital signs, complete blood count and electrolyteswere normal. An antiemetic was administered with resolu-tion of nausea. Warm blankets and active warm were im-plemented.One hour later, the boy was discharged from the recov-ery room. His vitals were stable and his TT was 34.5°C andhe was feeling more comfortable.The emergency team was called about 5 hours later be-cause the boy was still hypothermic (TT 34.0°C and axillartemperature (AT) 33.9°C) and sweating. Hyperglycemia re-mained (201 mg/dL). All his vitals were normal and his di-uresis was preserved (0.8 mL/kg/h). It was decided to warmthe patient with a forced air system, maintain clinical vigi-lance and hourly monitoring of temperature and capillaryglycemic values.Despite all the measures, temperature maintained be-low 36°C for the next 16 hours (33.8°C - 35.4°C), with grad-ual remission aapaapm of symptoms and normalization ofglycemic values.We excluded the most probable causes of post anes-thesia hypothermia (hypovolemia, environmental condi-tions or infection). His symptoms were considered to besecondary to the intrathecal morphine, as we consultedmedical literature and found that some similar cases havebeen reported in adult patients. Some of them used nalox-one or flumazenil to reverse symptoms successfully (2-6),however, our attitude was to maintain clinical vigilance. Inour clinical case, the symptoms disappeared 16 hours later,without pharmacotherapy, which favors that the cause ofhypothermia was due to intrathecal morphine.3. DiscussionThe core temperature (CT) is one of the most rigor-ously controlled physiological parameters of the body andis usually maintained within well-defined limits. The ther-moregulatory system allows small variations around 37°Cfor the maintenance of its optimal metabolic and homeo-static functions.Hypothermia is defined as a CT inferior to 36°C. CTmonitoring during anesthesia provides the early detectionof hypothermia that is associated with numerous compli-cations (7).The temperature of the skin changes according tothe temperature of the environment. However, the tem-perature of the deep tissues remain constant. This isachieved due to our thermoregulatory system, which isorganized into afferent pathways, integrative center, andefferent pathways, being that the hypothalamus is theprimary thermoregulatory center integrating the variousafferent inputs coordinating the responses required tomaintain normothermia. The exact way the body es-tablishes temperature thresholds is unknown, however,it is thought to involve post-synaptic inhibitory poten-tials modulated by various neurotransmitters such asnoradrenaline, dopamine, serotonin, acetylcholine, andprostaglandins. These thresholds vary daily around 0.15 to1°C with various factors, such as circadian rhythm, exercise,and infection. Upon integration, and if the temperature isoutside this inter-limb range, a response is triggered.In addition to exposure of the patient to the operat-ing room’s cold, the anesthetized patient is incapable oftriggering behavioral responses and is also prone to heatloss through the vasodilator action of anesthetic agents.The heat response threshold is usually well preserved dur-ing anesthesia, however, there is a marked linear decreasein the cold threshold with vasoconstriction and shiveringwhen opioids and volatile anesthetics are used. They alsohave a direct effect on the hypothalamus (7, 8).In SAB, redistribution is the main cause of hypother-mia in the surgical patient and is due to vasodilationcaused by sympathetic blockade. This effect is maximalduring the first 30 to 60 minutes and is dependent on theextent of the blockade. Another mechanism leading to hy-pothermia in these patients is the loss of thermoregula-tory vasoconstriction below the level of the blockade. Inpatients undergoing combined anesthesia, the risk of hy-pothermia will be higher, due to the shivering thresholddecrease and the inhibition of vasoconstriction induced byspinal anesthesia (7).All of these changes explain hypothermia during gen-eral or loco regional anesthesia, which can be easily pre-vented and reversible through active heating (gold stan-dard) (9).In the case of our patient, the hypothermia maintainedafter resolution of the sensory blockade, the absence of re-sponse to the heating measures performed, and the mal-adaptive response with sweating can’t be explained by sub-arachnoid blockade alone.2 Anesth Pain Med. 2018; 8(1):e66724.Ferraz S et al.After research in the literature, it was concluded thatthe hypothesis would most likely be intrathecal adminis-tration of morphine.The mechanism by which intrathecal morphine pro-duces this effect has not yet been fully elucidated. Someauthors have shown that spinal morphine has intensifiedhypothermia caused by subarachnoid anesthesia in preg-nant women submitted to cesarean section and in one caseafter an elective total knee arthroplasty. All of the patientscomplained about nausea and diaphoresis (2-6).It is known that opioids are directly involved in ther-moregulation and determine the temperature thresholdby interacting with the δ receptors in the hypothalamus,leading to poorly adaptive responses such as sweating thatmay exacerbate hypothermia and contribute to a falsesense of heat. The hypothermia and sweating observedin our patient may be related to the cephalic dispersionof morphine in the liquid cerebrospinal fluid due to itshydrophilic characteristics, leading to a disturbance ofthermoregulation after reaching the δ receptors in the hy-pothalamus.To solve the condition, some authors have successfullyadministered lorazepam, and it is thought that interactionwith GABA A receptors may have modulated thermoregula-tion in the hypothalamus. There is, however, no evidenceto support this approach (3, 4).Other authors have administered naloxone, which isa competitive antagonist of opioid receptors reversing itsaction. There was resolution of the picture, objectified bythe reduction of the sweating, and increase of the corporaltemperature after the administration of the same one (2, 5,6).3.1. ConclusionWe have concluded that if there is hypothermia in achild after a SAB and it does not respond to forced warm airheating, we should suspect that morphine injection maybe the leading cause, therefore, it is important to moni-tor intra and postoperative temperature when intrathecalmorphine is administered.FootnotesConflict of Interest: The authors declare no conflict of in-terest.Ethical Statement: All the authors meet the requirementsof authorship.References1. Ganesh A, Kim A, Casale P, Cucchiaro G. Low-dose intrathecalmorphine for postoperative analgesia in children. Anesth Analg.2007;104(2):271–6. doi: 10.1213/01.ane.0000252418.05394.28. [PubMed:17242079].2. Giladi Y, Ioscovich Y. hypothermia following intra-thecal morphineinjection during cesarean section a case report and literature review.J Anesth Clin Res. 2015;6(527).3. Ryan KF, Price JW, Warriner CB, Choi PT. Persistent hypothermia af-ter intrathecal morphine: case report and literature review. Can JAnaesth. 2012;59(4):384–8. doi: 10.1007/s12630-011-9650-z. [PubMed:22161244].4. Hess PE, Snowman CE, Wang J. Hypothermia after cesarean deliveryand its reversal with lorazepam. Int J Obstet Anesth. 2005;14(4):279–83.doi: 10.1016/j.ijoa.2005.02.004. [PubMed: 16143507].5. Sayyid SS, Jabbour DG, Baraka AS. Hypothermia and excessivesweating following intrathecal morphine in a parturient undergo-ing cesarean delivery. Reg Anesth Pain Med. 2003;28(2):140–3. doi:10.1053/rapm.2003.50043. [PubMed: 12677625].6. Mach J, Van Havel T, Gadwood J, Biegner MA. Intrathecal Opioid-Induced Hypothermia Following Subarachnoid Block With Mor-phine Injection for Elective Cesarean Delivery: A Case Report. AANAJ. 2016;84(1):23–6. [PubMed: 26939385].7. Sessler DI. Perioperative thermoregulation and heat balance.Lancet. 2016;387(10038):2655–64. doi: 10.1016/S0140-6736(15)00981-2.[PubMed: 26775126].8. Diaz M, Becker DE. Thermoregulation: physiological and clinicalconsiderations during sedation and general anesthesia. Anesth Prog.2010;57(1):25–32. quiz 33-4. doi: 10.2344/0003-3006-57.1.25. [PubMed:20331336].9. John M, Ford J, Harper M. Peri-operative warming devices: perfor-mance and clinical application. Anaesthesia. 2014;69(6):623–38. doi:10.1111/anae.12626. [PubMed: 24720346].Anesth Pain Med. 2018; 8(1):e66724. 3

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Persistent Hypothermia and Excessive Sweating Following Intrathecal Morphine Administration in a Teenage Boy: A Case Report

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