Conference Lectures

Emergence agitation in patients undergoing Adenotonsillectomy
                                                                                        

Dr. Usha Shukla
Addl. Prof.
U.P RIMS & R Saifai
ETAWAH

Paediatric surgery usually has shorter operation times, length of stay and less complications hence the recovery time and postoperative complications are important indicators for the evaluation of paediatric anaesthesia.
Before the development of most of the modern inhalational anaesthetic agents, postoperative agitation was a feature of general anaesthesia but many studies found that the incidence of postoperative agitation has increased since the introduction of the less soluble inhalational agents e.g desflurane and sevoflurane into routine anaesthesia practice .
Eckenhoff 1 et al first reported the phenomenon of emergence agitation in 1961. They reviewed 14,436 patients and found statistically higher incidence of emergence agitation to be associated with four factors i.e (1) children 3-9 years (2) Ether or cyclopropane anaesthesia (3) Tonsillectomy (4) Barbiturate premedication. They also found that in patients who received intraoperative opioids the incidence of emergence agitation was reduced.
Gradually cyclopropane and ether were discontinued or the use was reduced over a period of time, the use of halothane became more common. For decades, halothane was administered in children as predominant inhalational anaesthetic agent. The incidence of emergence agitation was attenuated with the use of postoperative analgesic in children and role of adequate pain management was recognised. But after the introduction of new, short acting, poor  lipid soluble volatile anaesthetic agents in clinical practice , the problem of emergence agitation again emerged.
Definition :  A variety of behavioural disturbances can be experienced by a child upon emergence from anaesthesia. These disturbances are interchangeably described as post anaesthetic excitation, 2 delirium or emergence agitation. But clinical presentation and definitions of agitation and delirium are different.
Agitation is a state of non-purposeful restlessness and inconsolability which is accompanied by screaming, trashing, persistent and prolonged crying and disorientation. Children exhibiting emergence agitation are not aware of their surroundings and unable to be consoled by the caregiver or parent. Agitation, a state of mental distress is very common in postoperative period in children as well as in adults. Pain, anxiety or any discomfort may cause agitation.3 Agitation occurring due to pain and anxiety can be treated with reassurance, analgesia and benzodiazepines.
Delirium, a complex psychiatric syndrome includes cognitive impairment, hallucinations and psychomotor agitation.4 Delirium is more difficult to diagnose, prevent and treat and has much different outcome. Emergence delirium usually occurs within first half an hour of recovery from anaesthesia and resolves spontaneously5, 6 more often, while agitation and regressive behaviour may last up to two days postoperatively.
The distinction of cognitive impairment critical to make correct diagnosis and providing appropriate therapy for emergence agitation is difficult to differentiate in children so the terms emergence agitation and delirium are used interchangeably.
Children suffering from severe emergence reactions may get harmed during the periods of inconsolability , trashing and may pull drains, intravenous catheters, nasogastric tubes and other monitoring, medical devices essential for their care.
Etiological factors contributing to emergence agitation:

  1. Patient related factors:
  2. Age:  Aono7 et al in 1997 showed that emergence agitation appears in preschool boys aged 2-6 years at higher rate than school aged population. The authors attributed this to psychological immaturity of preschool children along with rapid awakening in a strange environment.

Martini8 in a recent commentary addressed the role of brain maturation in the occurrence of this phenomenon and suggested the role of physiological development to the susceptibility of preschool group to delirium.

  1. Pre- operative anxiety : Various groups9,10 studied the co-relation between preoperative anxiety and postoperative agitation. In a retrospective data base search of 791 children , Kain11 et al showed that high levels of preoperative anxiety is associated with development of postoperative adverse behaviour including emergence delirium. With increment of 10 points in children’s state anxiety score the odds of emergence delirium increased by 10% approximately. The relation between parental anxiety an emergence delirium could not be demonstrated by them. Fortier12 et al in 2010 demonstrated that parental anxiety could be a contributing factor to emergence delirium as it was a risk factor for high levels of child’s anxiety from the preoperative holding area to the perioperative settings and up to 2 weeks postoperatively.

Voepel2 et al however in his prospective study showed that preoperative      anxiety has no association with postoperative emergence agitation in paediatric post anaesthesia care unit (PACU).
(C) Parental presence in post anaesthesia care unit (PACU) : Many studies13,14,15 were done which observed the preoperative anxiety of parent prior to induction of anaesthesia and effects of these factors on child’s emergence agitation.But only few studies focus on the effects of parental presence as the child awakens in PACU. Demirbilek14 et al & Aouad15 et al showed the low incidence of emergence agitation in children, while their parents were present in PACU,in presence14 or absence15 of surgical pain. This positive effect of parental presence was not the studied outcome but was only noticeable observation.
(d) Child’s temperament-  Children who were less sociable, more impulsive and emotional & less adaptive to environmental changes showed higher incidence of emergence agitation11 so this innate temperament of the child who are to be anaesthetized might cause emergence agitation.16
(2) Anaesthesia related factors- Many studies were done to evaluate the incidence of emergence agitation following inhalational or intravenous anaesthetic agents . The less soluble newer inhaled anaesthetics eg.-Sevoflurane, Desflurane are found to be associated more with postanaesthetic agitation. Studies2, 17 found that both Desflurane and Isoflurane have comparable incidence of emergence agitation ranging between 50% - 80%. Freye18 et al found that EEG changes in patients under Sevoflurane were similar to patients under Isoflurane & Desflurane. Many studies19, 20 however showed that sevoflurane is associated more with emergence agitation than halothane with different EEG changes.
                                The rapid emergence following sevoflurane anaesthesia was postulated to be the cause of emergence agitation. Regaining consciousness in an unfamiliar environment could be the cause of emergence agitation. Patients like preschool children have less ability to cope with environment.
Many studies21, 22 were done to compare sevoflurane and propofol on the quality of recovery. Cohen23 et al studied the emergence from sevoflurane & propofol anaesthesia which allows faster recovery and found that as compared to sevoflurane the rapid emergence from propofol was smooth & pleasant. They concluded that speed of recovery is not related to emergence agitation. Oh24 et al found that incidence of emergence agitation did not reduce by delaying emergence by stepwise decrease of sevoflurane.  Hence emergence agitation could be related to the intrinsic property of inhalational anaesthetics but not with rapid emergence.

  1. Surgery related factors-
  2. Type of procedure- Surgical procedures which involve the tonsils, eyes, ear thyroid and urological procedures are associated with higher incidence of emergence agitation. In 1961, Eckenhoff1 et al found “ sense of suffocation “ as the cause of increased incidence of emergence agitation among otolaryngologic procedures. In a prospective study in 2003, Voepel-lewis2 showed that the otolaryngologic procedures an independent risk factors for emergence agitation.
  3. Pain: On assessing a child’s behaviour upon emergence, postoperative pain is the most compounding variable. Many studies were carried out to study the casual effect pain and emergence agitation and treating pain with different modalities e.g NSAID’S, α-2 agonists e.g clonidine, dexmedetomidine, regional anaesthesia like caudal blocks to decrease the incidence of emergence agitation. It was observed in these studies  that although the incidence of emergence had decreased after adequate pain relief as compared to controls but not abolished, suggesting the presence of emergence agitation even after adequate pain relief.

            Cravero25 et al studied children undergoing non painful interventions such as MRI and found higher incidence of emergence agitation in patients anaesthetized with sevoflurane compared with halothane. Hence, pain cannot  be blamed as sole contributing factor to emergence agitation.
Prevention & Treatment: To ameliorate the disturbances caused by emergence agitation both prophylactic and postoperative treatments have been studied. Depending on the time of administration, propofol delays, modifies and decreases emergence agitation. Aouad26 et al found that propofol when administered (1mg/kg) at the end of surgery decreases the emergence agitation because of effective plasma concentration of propofol. Midazolam administered as premedication does not consistently decrease the emergence agitation.In study by Viitanen27 et al, midazolam led to increase in emergence agitation as compared to placebo.
Cohen28 et al observed patients undergoing adenoidectomy under desflurane anaesthesia and found no advantage of either propofol or midazolam intravenous in reducing emergence agitation.
Fentanyl , α-2 adrenergic agonists e.g clonidine, dexmedetomidine, ketamine are found to be effective measures in reducing the emergence reactions.
Many studies23,29,30 showed that fentanyl decreases emergence reactions in patients following sevoflurane and desflurane anaesthesia as it has high efficacy as preoperative analgesia as well as sedative effects. Carvaro30 et al found the incidence to decrease from 56% to 12% in patients undergoing MRI, when fentanyl 1mg/kg was given intravenously, 10 minutes before discontinuation of anaesthetic agents.
Isik31, 32, 33 et al administered dexmedetomidine 0.3-1µg/kg after induction of anaesthesia and found reduced incidence of emergence agitation between 4.8% & 17% with no hamodynamic effects. Dexmedetomidine has sedative, analgesic and anxiolytic effects on I/V administration.
α-2 agonists decrease emergence agitation not only due to their analgesic effects but also by decreasing anaesthetic requirements. Bock33 et al documented the decrease in emergence agitation after clonidine administered I/V after induction, they also noted that this effect of clonidine is independent of route of administration be it I/v or caudal.
Ketamine, a NDMA receptor antagonist has both analgesic and opioids sparing effects in low doses. Dalens34 et al administered ketamine 0.25 mg/kg at the end of MRI in children and found reduced agitation and no delay in discharge.
Most adjuvants decrease emergence agitation through their analgesic and sedative effects in painful or non-painful procedures. Dahmani35 et al in a recent metaanalysis showed that propofol, opioids e.g fentanyl, ketamine, α-2 agonists and pain prevention have preventive effects on emergence delirium but midazolam & serotonin inhibitors did not.
Non pharmacologic tools:
(1) Maintain quiet environment for the child.

  1. Reunite the child with parent during emergence.
  2. Holding the child and physical restraint preferably by parent.

Long term consequences:  Long term maladaptation can be found in children following anaesthesia. It can be related to duration and type of anaesthetic, hypnotic depth and incidence of EA. Many studies found no conclusive relationship between length of time & deep hypnosis, 36 type of anaesthetic & maladaptive behaviour.37 So keeping in view of the results of these studies, a theory associating emergence agitation & long term maladaptive behaviour or type of anaesthetic & behavioural changes cannot be established.
Summary: A young, preschool anxious child undergoing painful procedure of short duration with inadequate pain control is most likely to suffer from emergence agitation. Poorly soluble inhalational anaesthetic agents e.g sevoflurane, desflurane and isoflurane are associated with high incidence of postoperative agitative behaviour even if there is no pain. Halothane & propofol are least associated with EA. Fentanyl, α-2 agonists , ketamine are effective in reducing the symptoms of EA when used as preemptive medication.
The direct pharmacological action or delay in awakening caused by sedative action of these drugs ameliorating the postoperative agitation, is not clear.

References:

  1. Eckenhoff JE, Kneale DH, Dripps RD. The incidence and etiology of postanaesthetic excitement: a clinical survey. Anesthesiology 1961:22;667-73.
  2. Voepel-Lewis T, Malviya S, Tait AR. A prospective cohort study of emergence agitation in the pediatric postanesthesia care unit. Anesth analg 2003;96:1625-30.
  3. Voepel-Lewis T, Burke C. differentiating pain and delirium is only part of assessing the agitated child. J Perianesth Nurs 2004;19:298-9.
  4. American Psychiatric association. Diagnostic and statistical manual of mental disorders. 4th ed.arlington, VA: American Psychiatric Publishing,2000.
  5. Olympio MA. Postanesthetic delirium: historical perspectives. J clin anesth 1991;3:60-3.
  6. Moore Jk, Moore EW, Elliot RA, et al. Propofol and halothane versus sevoflurane in pediatric day case surgery: induction and recovery characteristics. Br J Anaesth 2003;90:461-6.
  7. Aono J, Ueda W, Mamiya K , Takimoto E, Manabe M. Greater incidence of delirium during recovery fromsevoflurane in preschool boys. Anesthesiology1997;87:1298-300.
  8. Martini DR. Commentary: the diagnosis of delirium in paediatric patients. J Am Acad Child Adolesc psychiatry 2005;44:395-8.
  9. Kain ZV, Mayes LC, O’Connor TZ, Cicchtti DV: Preoperative anxiety in children; predictors and outcomes. Arch Pediatr adolesc Med; 1996;150:1238-45.
  10. Aono J, Mamiya K, Manabe M: Preoperative anxiety is associated with a high incidence of problematic behaviour on emergence after halothane anesthesia in boys. Acta anaesthesiol Scand; 1999:43:542-4.
  11. Kain Z, Caldwell- Andrews A, Maranetes I,McClain B, Gaal D, Mayes LC et al. Preoperative anxiety and emergence delirium and postoperative maladaptive behaviors. Anesth analg;2004;99:1648-54.
  12. Fortier MA, Del Rosario A, Martin S, KainZN. Perioperative anxiety in children. PediatrAnesth;2010:318-22.
  13. Weldon BC, Bell M, Craddock T: The effect of caudal analgesia on emergence agitation in children after sevoflurane versus halothane anesthesia. Anesth Analg; 98:321-26.
  14. Demirbilek S, Togal T, Cicek M, Alan U, Sizanli E, Ersoy MO: Effects of fentanyl on the incidence of emergence agitation in children receiving desflurane Vs sevoflurane anesthesia. Eur. J.Anaesthesiol;2004;21:538-42.
  15. Aouad MT, Kanzai GE, Siddik-sayyid SM, Gerges FJ, Rizk LB, Baraka AS. Preoperative caudal block prevents emergence agitation in children following sevoflurane anesthesia. Acta Anaesthesiol Scand 2005;49:300-4.
  16. Rothbart MK, Ahadi SA, Evans DE. Temprament and personality: origins and outcomes. J Pres Soc Psychol  2000;78:122-35.
  17. Cole J, Murry D, Mcallister J, Hirshberg G. Emergence behaviour in children defining the incidence of excitement and agitation following anesthesia. Pediatr Anaesth 2002; 12:442-7.
  18. Freye E, Bruckner J, Latsch L. No difference in electroencephalographic power spectra or sensory evoked potentials in patients anesthetised with desflurane or sevoflurane. Eur j anaesthesiol 2004;21:373-8.
  19. Bajwa SA, Costi D, Cyna AM. A comparison of emergence delirium scales following general anesthesia in children. Pediatric Anesthesia 2010;20:704-11.
  20. Constant I, Dubois MC, Piat V, Moutard ML, McCue M, Murat I. Changes in electroencephalogram and autonomic cardiovascular activity during induction of anesthesia with sevoflurane compared with halothane in children. Anesthesiology 1999;91:1604-15.
  21. Picard V, Dumont L, Pelligrini M. Quality of recovery in children : sevoflurane Vs propofol Acta anaesthesiol Scand 2000; 44:307-10.
  22. Uezono S, Goto T, Terui K, Ichinose F, Ishguro Y, Nakata Y, Morita S. Emergence agitation after sevoflurane Vs propofol in pediatric patients Anesth Analg; 2000; 91:563-66.
  23. Cohen IT, Finkel JC, Hannallah KA, Patel KM. Rapid emergence does not explain agitation following sevoflurane anesthesia in infants and children: a comparison with propofol. Paediatr Anaesth 2003; 13:63-67.
  24. Oh A, Seo k, Kim C, kim H: Delayed emergence process does not result in lower incidence of emergence agitation sevoflurane anesthesia in children. Acta Anaesthesiol scand 2005;49:297-99.
  25. Cravero J, Surgenor S, Whalen K. Emergence agitation in paediatric patients after sevoflurane anesthesia and no surgery: a comparison with halothane. Pediatr Anaesth 2000;10:419-24.
  26. Aouad MT, Yazbeck- Karam VG, Nasr VG, El- Khatib MF, Kanzai GE,Bleik JH. A single dose of propofol at the end of surgery for the prevention of emergence agitation in children undergoing strabismus surgery during sevoflurane anesthesia. Anesthesiology 2007;107:733-8.
  27. Viitanen H, Annila P, Viitanen M et al. midazolam premedication delays recovery from propofol –induced sevoflurane anesthesia in children 1-3 years. Can J anaesth 1999;46:766-71.
  28. Cohen IT, Drewsen S, Hannallah RS. Propofol or midazolam do not reduce incidence of emergence agitation associated with desflurane anesthesia in children undergoing adenotonsillectomy. Paediatr anaesth 2002;12:604-9.
  29. Cohen IT, Hannallah RS, Hummer KA. The incidence of emergence agitation associated with desflurane anesthesia in children is reduced by fentanyl. Anesth Analg 2001;93:88-91.
  30. Cravero JP, Beach M, Thyr B, Whalen K. The effect of small dose fentanyl on the emergence characterstics of pediatric patients after sevoflurane anesthesia without surgery. Aesth Analg 2003;97:364-7.
  31. Guler G, Akin A, Tousun Z, Ors S, Esmaoglu a, Boyaci A. Single dose dexmedetomidine reduces agitation and provides smooth extubation after pediatric adenotonsillectomy. Pediatr annesth 2005;15:762-66.
  32. Isik B, Arselan M, Tunga AD, Kurtipek O. Dexmedetomidine decreases emergence agitation in pediatric patients after sevoflurane anesthesia without surgery. Pediatr anesth 2006;16:748-53.
  33. Bock M, Kunz P, Schreckenberger R, Graf BM, Martin E, Motsch J. comparison of caudal and intravenous clonidine in the prevention of agitation after sevoflurane in children. Br J Anaesth 2002;88:790-6.
  34. Dalens BJ ,Pinard AM, Letournea DR, Albert NT, Truchon RJY. Prevention of emergence agitation after sevoflurane anesthesia for pediatric cerebral magnetic resonance imaging by small doses of ketamine or nalbuphine administered just before discontinuing anesthesia. Anesth analg 2006;102:1056-61.
  35. Dahmani S, Stany I, Brasher C, Lejeune C, Bruneau B, Wood C et al Pharmacological prevention of sevoflurane and desflurane related emergence agitation in children : a meta analysis of published studies. Br J Anaesth 2010;104:216-23.
  36. Faulk Dj, Twite MD, Zuk J, Pan Z, Wallan B, Frisen RH. Hypnotic depth and the incidence of emergence agitation and negative postoperative behavioural changes. Pediatr Anesth 2010;20:72-81.
  37. Keany A, Divney D, Harte S, Lyons B. Postoperative behavioural changes following anesthesia with sevoflurane. Pediatr Anesth 2004;14:866-70.