N Sikich

SickKids, Toronto, Ontario, Canada

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Publications (41)153.32 Total impact

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    ABSTRACT: The current standard of care for fluid resuscitation of hemorrhagic hypotensive patients involves the use of crystalloid solutions. Traumatic brain injury (TBI) is often associated with hemorrhage and hypotension, which can contribute significantly to morbidity and mortality. Guidelines for the choice of fluid resuscitation and the use of red blood cell transfusions are not yet clear in the context of brain injury. Various fluid resuscitation strategies were evaluated in Sprague-Dawley rats using fresh blood, normal saline, hypertonic saline, and albumin fluid resuscitation protocols. Mean arterial blood pressure (MAP) and cerebral oximetry were assessed in hemorrhaged groups and the mean population spike amplitudes (PSA) from the hippocampus were examined in fluid percussion injured (FPI) animals subject to hemorrhage and fluid resuscitation. MAP in control animals, hemorrhage and hemorrhage + albumin treated groups was 82.4 +/- 1.5 mm Hg, 55.7 +/- 1.5 mm Hg, and 97.0 +/- 3.4 mm Hg, respectively. Arterial PaO2 was higher in albumin-treated animals relative to other fluid alternatives. Regional tissue oxygen tension (PbrO2) levels in hemorrhaged animals reached significantly higher levels in albumin treated group compared with in normal saline and hypertonic saline (p < 0.001, p = 0.034, respectively). After FPI+hemorrhage, PSA values in albumin- resuscitated animals were significantly higher than in normal saline-resuscitated animals (p = 0.012). The results of normal saline resuscitation, relative to other fluid alternatives, suggest that a re-evaluation of current treatment strategies in hemorrhagic hypotensive TBI patients is warranted. Albumin demonstrated the greatest beneficial effects on neurophysiology endpoints over crystalloid alternatives. These data suggests that albumin resuscitation may play an important role in the treatment of hemorrhagic hypotension and TBI.
    The Journal of trauma 03/2008; 64(2):348-57. · 2.35 Impact Factor
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    ABSTRACT: Anemia may worsen neurological outcomes following traumatic brain injury (TBI) by undefined mechanisms. We hypothesized that hemodilutional anemia accentuates hypoxic cerebral injury following TBI. Anesthetized rats underwent unilateral TBI or sham injury (n > or = 7). Target hemoglobin concentrations between 50 and 70 g/l were achieved by exchanging 40-50% of the blood volume (1:1) with pentastarch. The effect of TBI, anemia, and TBI-anemia was assessed by measuring brain tissue oxygen tension (Pbr(O(2))), regional cerebral blood flow (rCBF), jugular venous oxygen saturation (Sjv(O(2))), cerebral contusion area, and nuclear staining for programmed cell death. Baseline postinjury Pbr(O(2)) values in the TBI and TBI-anemia groups (9.3 +/- 1.3 and 11.3 +/- 4.1 Torr, respectively) were lower than the uninjured controls (18.2 +/- 5.2 Torr, P < 0.05 for both). Hemodilution caused a further reduction in Pbr(O(2)) in the TBI-anemia group relative to the TBI group without anemia (7.8 +/- 2.7 vs. 14.8 +/- 3.9 Torr, P < 0.05). The rCBF remained stable after TBI and increased comparably after hemodilution in both anemia and TBI-anemia groups. The Sjv(O(2)) was elevated after TBI (87.4 +/- 8.9%, P < 0.05) and increased further following hemodilution (95.0 +/- 1.6%, P < 0.05). Cerebral contusion area and nuclear counts for programmed cell death were increased following TBI-anemia (4.1 +/- 3.0 mm(2) and 686 +/- 192, respectively) relative to TBI alone (1.3 +/- 0.3 mm(2) and 404 +/- 133, respectively, P < 0.05 for both). Hemodilutional anemia reduced cerebral Pbr(O(2)) and oxygen extraction and increased cell death following TBI. These results support our hypothesis that acute anemia accentuated hypoxic cerebral injury after neurotrauma.
    Journal of Applied Physiology 09/2007; 103(3):1021-9. · 3.48 Impact Factor
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    ABSTRACT: The aim of this study was to describe a comprehensive continuum that has developed in Ontario between government and key stakeholder groups, including hospitals, physicians, academic institutions, clinical epidemiologists, health economists, industry, and bioethicists to achieve evidence-based recommendations for policy development. The various components of the comprehensive model that has evolved to develop an evidentiary platform for policy development are summarized, and the flow between these components is described. The development of the Ontario Health Technology Advisory Committee (OHTAC) and associated programs demonstrate the need to go beyond the traditional steps taken within most health technology assessment paradigms. These components include pragmatic postmarketing studies, human factors, and safety analyses, and formalized interactions with a broad spectrum of potential end-users of each technology, experts, and industry. Thesecomponents, taken together with an expanded systematic review to include a range of economic analyses, and societal impacts augment the traditional systematic review processes. This approach has been found to be important in assisting decision making and has resulted in an 81 percent conversion from evidence to policy consideration for eighty-three technologies that had been assessed at the time this article was submitted. The comprehensive model, centered around OHTAC, has added important new dimensions to health policy by improving its relevance to decision makers and providing an accountable and transparent basis for government to invest appropriately in health technologies. This study could also form a basis for further research into appropriate methodologies and outcome measurements as they relate to each component of this approach.
    International Journal of Technology Assessment in Health Care 02/2007; 23(3):299-309. · 1.55 Impact Factor
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    ABSTRACT: To investigate dexmedetomidine in children, the authors performed an open-label study of the pharmacokinetics and pharmacodynamics of dexmedetomidine. Thirty-six children were assigned to three groups; 24 received dexmedetomidine and 12 received no drug. Three doses of dexmedetomidine, 2, 4, and 6 microg x kg x h, were infused for 10 min. Cardiorespiratory responses and sedation were recorded for 24 h. Plasma concentrations of dexmedetomidine were collected for 24 h and analyzed. Pharmacokinetic variables were determined using nonlinear mixed effects modeling (NONMEM program). Cardiorespiratory responses were analyzed. Thirty-six children completed the study. There was an apparent difference in the pharmacokinetics between Canadian and South African children. The derived volumes and clearances in the Canadian children were V1 = 0.81 l/kg, V2 = 1.0 l/kg, Cl1 (systemic clearance) = 0.013 l x kg x min, Cl2 = 0.030 l x kg x min. The intersubject variabilities for V1, V2, and Cl1 were 45%, 38%, and 22%, respectively. Plasma concentrations in South African children were 29% less than in Canadian children. The volumes and clearances in the South African children were 29% larger. The terminal half-life was 110 min (1.8 h). Median absolute prediction error for the two-compartment mammillary model was 18%. Heart rate and systolic blood pressure decreased with time and with increasing doses of dexmedetomidine. Respiratory rate and oxygen saturation (in air) were maintained. Sedation was transient. The pharmacokinetics of dexmedetomidine in children are predictable with a terminal half-life of 1.8 h. Hemodynamic responses decreased with increasing doses of dexmedetomidine. Respiratory responses were maintained, whereas sedation was transient.
    Anesthesiology 01/2007; 105(6):1098-110. · 5.16 Impact Factor
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    ABSTRACT: Haemodilution has been associated with neurological morbidity in surgical patients. This study tests the hypothesis that inhibition of cerebral vasodilatation by systemic beta2 adrenergic blockade would impair cerebral oxygen delivery leading to tissue hypoxia in severely haemodiluted rats. Under general anaesthesia, cerebral tissue probes were placed to measure temperature, regional cerebral blood flow (rCBF) and tissue oxygen tension (P(Br)O2) in the parietal cerebral cortex or hippocampus. Baseline measurements were established before and after systemic administration of either a beta2 antagonist (10 mg kg(-1) i.v., ICI 118, 551) or saline vehicle. Acute haemodilution was then performed by simultaneously exchanging 50% of the estimated blood volume (30 ml kg(-1)) with pentastarch. Arterial blood gases (ABGs), haemoglobin concentration (co-oximetry), mean arterial blood pressure (MAP) and heart rate (HR) were also measured. Data were analysed using a two-way anova and post hoc Tukey's test [mean (sd)]. Haemodilution reduced the haemoglobin concentration comparably in all groups [71 (9) g litre(-1)]. There were no differences in ABGs, co-oximetry, HR and MAP measurements between control and beta2 blocked rats, either before or 60 min after drug or vehicle administration. In rats treated with the beta2 antagonist there was a significant reduction in parietal cerebral cortical temperature, regional blood flow and tissue oxygen tension, relative to control rats, 60 min after haemodilution (P<0.05 for each). These differences were not observed when probes were placed in the hippocampus. Systemic beta2 adrenergic blockade inhibited the compensatory increase in parietal cerebral cortical oxygen delivery after haemodilution thereby reducing cerebral cortical tissue oxygen tension.
    BJA British Journal of Anaesthesia 12/2006; 97(5):617-23. · 4.24 Impact Factor
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    ABSTRACT: Background: To investigate dexmedetomidine in children, the authors performed an open-label study of the pharmacokinetics and pharmacodynamics of dexmedetomidine.
    Anesthesiology 11/2006; 105(6):1098-1110. · 5.16 Impact Factor
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    Canadian Journal of Anaesthesia 01/2005; 52. · 2.13 Impact Factor
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    Canadian Journal of Anaesthesia 01/2005; 52. · 2.13 Impact Factor
  • Nancy Sikich, Jerrold Lerman
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    ABSTRACT: Emergence delirium has been investigated in several clinical trials. However, no reliable and valid rating scale exists to measure this phenomenon in children. Therefore, the authors developed and evaluated the Pediatric Anesthesia Emergence Delirium (PAED) scale to measure emergence delirium in children. A list of scale items that were statements describing the emergence behavior of children was compiled, and the items were evaluated for content validity and statistical significance. Items that satisfied these evaluations comprised the PAED scale. Each item was scored from 1 to 4 (with reverse scoring where applicable), and the scores were summed to obtain a total scale score. The degree of emergence delirium varied directly with the total score. Fifty children were enrolled to determine the reliability and validity of the PAED scale. Scale validity was evaluated using five hypotheses: The PAED scale scores correlated negatively with age and time to awakening and positively with clinical judgment scores and Post Hospital Behavior Questionnaire scores, and were greater after sevoflurane than after halothane. The sensitivity of the scale was also determined. Five of 27 items that satisfied the content validity and statistical analysis became the PAED scale: (1) The child makes eye contact with the caregiver, (2) the child's actions are purposeful, (3) the child is aware of his/her surroundings, (4) the child is restless, and (5) the child is inconsolable. The internal consistency of the PAED scale was 0.89, and the reliability was 0.84 (95% confidence interval, 0.76-0.90). Three hypotheses supported the validity of the scale: The scores correlated negatively with age (r = -0.31, P <0.04) and time to awakening (r = -0.5, P <0.001) and were greater after sevoflurane anesthesia than halothane (P <0.008). The sensitivity was 0.64. These results support the reliability and validity of the PAED scale.
    Anesthesiology 06/2004; 100(5):1138-45. · 5.16 Impact Factor
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    ABSTRACT: Few studies have examined whether nitrous oxide influences the recovery characteristics of propofol anaesthesia. The present study examined the effect of nitrous oxide on the recovery characteristics of propofol anaesthesia, and compared these data with those for halothane/nitrous oxide anaesthesia. Sixty children aged 3–12 years were assigned at random to receive one of three maintenance regimens: propofol with or without nitrous oxide (70%) or halothane/nitrous oxide (70%). During propofol/N2O anaesthesia, the infusion rate of propofol (180±39 μg·kg−1·min−1) required to maintain the mean arterial pressure and heart rate within 20% of the baseline values was significantly less than that during propofol/O2 (220±37 μg·kg−1·min−1; P<0.005). The time from discontinuation of anaesthesia to eye-opening (11±6 min), to response to commands (12±6 min), and to return of full wakefulness (21±10 min) after propofol/N2O were similar to those after propofol/O2, but significantly less (by approximately 30%) than those after halothane (P<0.05). The overall incidence of emesis after propofol/N2O (53%) was greater than that after propofol/O2 (17%, P<0.05) and comparable to that after halothane/N2O (58%). These data suggest that N2O has little effect on the rate of recovery after propofol, but significantly increases the incidence of postoperative emesis, thereby attenuating one of the main attributes of propofol anaesthesia.
    Pediatric Anesthesia 01/2002; 8(1):49 - 54. · 2.44 Impact Factor
  • N Sikich, J Lerman
    Journal of Clinical Anesthesia 04/2001; 13(2):157-8. · 1.15 Impact Factor
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    ABSTRACT: Epidural infusions of fentanyl (2 micrograms.ml-1) alone or combined with bupivacaine 0.125% were compared for perioperative analgesia, motor block and other side-effects in children who underwent urological surgery. In a prospective, double-blind study, 42 children, ASA I-II, 1-16 yr, were randomly allocated to receive either epidural F (fentanyl bolus 2 micrograms.kg-1 in 0.5 ml.kg-1 saline followed by 2 micrograms.ml-1 fentanyl infusion) or epidural F-B (fentanyl bolus 2 micrograms.kg-1 in 0.5 ml.kg-1 bupivacaine 0.25% followed by 2 micrograms.ml-1 fentanyl infusion in bupivacaine 0.125%) after induction of general anaesthesia. Adequacy of analgesia, lower limb motor block and side-effects were assessed four hourly postoperatively. Both infusion regimens provided excellent analgesia (median objective pain scores = 0). Epidural infusion rates were similar in the F (0.29 +/- 0.07 ml.kg-1.hr-1) and F-B (0.26 +/- 0.05 ml.kg-1.hr-1) groups. Three children in the F group and all children in the F-B group developed lower limb weakness. (P < 0.05) Bromage scores were different in the F group (median 0, range 0-0.66) compared with the F-B group (median 0.33, range 0-1) (P < 0.001). Other side-effects did not differ. Postoperative epidural fentanyl infusion provides equipotent analgesia to administration of a solution including both fentanyl and bupivacaine 0.125% and causes less lower limb weakness. No reduction in the fentanyl requirement resulted from the addition of bupivacaine 0.125%.
    Canadian Journal of Anaesthesia 12/1998; 45(11):1054-60. · 2.13 Impact Factor
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    ABSTRACT: To compare the maintenance and recovery characteristics after sevoflurane with those after propofol in children with epidural blockade. Fifty unpremedicated, children ASA I-II, 2-8 yr of age, scheduled for elective urological surgery as outpatients, were randomly allocated to receive either: 1) sevoflurane for induction and maintenance of anaesthesia or 2) propofol for induction (2-3 mg.kg-1 i.v.) and for maintenance (5-10 mg.kg-1.hr-1 i.v.). All children received N2O 70% in oxygen before induction and throughout the anaesthetic, rocuronium for neuromuscular blockade and a lumbar or caudal epidural block before incision. Heart rate (HR), systolic blood pressure (SBP), recovery times and all side effects during maintenance and recovery were recorded by a blinded observer. Adverse events during the first 24 hr were also recorded. Mean HR increased 5-10% after induction in both groups reaching a maximum by five minutes. Heart rate returned to baseline by skin incision in the sevoflurane group and by 10 min after induction in the propofol group. During maintenance, HR decreased by 10-20% below baseline values by 20 min in the propofol group only, where it remained for the remainder of the anaesthetic. Similarly, SBP increased by 10% after induction of anaesthesia in both groups, but returned to baseline by 10 min. Light anaesthesia occurred in four (16%) children, all in the propofol group. Emergence and recovery indices were similar in the two groups. Sevoflurane and propofol exhibit similar maintenance and recovery profiles when combined with epidural analgesia in children undergoing ambulatory surgery.
    Canadian Journal of Anaesthesia 12/1998; 45(11):1072-8. · 2.13 Impact Factor
  • R C Agnor, N Sikich, J Lerman
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    ABSTRACT: The authors compared the speed of induction of anesthesia with sevoflurane with and without nitrous oxide with the speed of halothane and nitrous oxide using a single-breath vital capacity induction. With informed parental consent, 51 healthy unpremedicated children aged 5-12 yr were randomized to inhale a single breath of one of three gas mixtures: 8% sevoflurane in 66% nitrous oxide, 8% sevoflurane in oxygen, or 5% halothane in 66% nitrous oxide. A blinded observer recorded the times to loss of the eyelash reflex, return of conjugate gaze, the presence of airway reflex responses, involuntary movement, and hemodynamic responses. Forty-two children completed the study. The times (mean +/- SD) to loss of the eyelash reflex with sevoflurane/nitrous oxide, 38+/-8 s, and for sevoflurane-oxygen, 34+/-12 s, were less than that with halothane-nitrous oxide, 58+/-17 s (P < 0.01). Movement occurred less frequently during sevoflurane than during halothane anesthesia (P < 0.05). The times to return of conjugate gaze and the incidence of airway reflex responses were similar among the groups. The incidence of dysrhythmias in the sevoflurane groups was less than that in the halothane group (P < 0.01). Induction of anesthesia with a single breath of 8% sevoflurane with or without 66% nitrous oxide is more rapid than with 5% inspired halothane with 66% nitrous oxide in children. The incidence of movement and dysrhythmias during a single-breath induction with sevoflurane are less than they are with halothane.
    Anesthesiology 08/1998; 89(2):379-84. · 5.16 Impact Factor
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    ABSTRACT: We compared the effectiveness of ondansetron, dimenhydrinate, and placebo for the prevention of postoperative vomiting in children after adenotonsillectomy. In a randomized, placebo-controlled, double-blind study, 74 children, 2-10 yr of age scheduled for adenotonsillectomy as outpatients were given a single i.v. dose of ondansetron (0.1 mg/kg, n = 26), dimenhydrinate (0.5 mg/kg, n = 25), or placebo (saline, n = 23) at induction of anesthesia. The incidence of retching and vomiting (POV) and side effects observed 24 h after surgery were recorded. Demographic data were similar among the three groups. The 24-h incidence of POV was 42%, 79%, and 82% in the ondansetron, dimenhydrinate, and placebo groups, respectively (ondansetron compared with dimenhydrinate [P < 0.02] or placebo [P < 0.01]). The study was stopped after two children vomited large volumes of bloody fluid 9 and 22 h after surgery without previous signs of occult bleeding. Both children had received ondansetron. We conclude that ondansetron is superior to dimenhydrinate or placebo for the prevention of POV after adenotonsillectomy in children. Antiemetics may mask the signs of bleeding after adenotonsillectomy. IMPLICATIONS: I.v. ondansetron (0.1 mg/kg) is more effective than both dimenhydrinate and placebo in preventing vomiting after adenotonsillectomy in healthy children. However, antiemetics may also mask the presence of blood in the stomach by preventing vomiting, and this should be appreciated when adenotonsillectomy is performed on an outpatient basis.
    Anesthesia & Analgesia 03/1998; 86(3):496-500. · 3.30 Impact Factor
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    ABSTRACT: Few studies have examined whether nitrous oxide influences the recovery characteristics of propofol anaesthesia. The present study examined the effect of nitrous oxide on the recovery characteristics of propofol anaesthesia, and compared these data with those for halothane/nitrous oxide anaesthesia. Sixty children aged 3-12 years were assigned at random to receive one of three maintenance regimens: propofol with or without nitrous oxide (70%) or halothane/nitrous oxide (70%). During propofol/N2O anaesthesia, the infusion rate of propofol (180 +/- 39 micrograms.kg-1.min-1) required to maintain the mean arterial pressure and heart rate within 20% of the baseline values was significantly less than that during propofol/O2 (220 +/- 37 micrograms.kg-1.min-1; P < 0.005). The time from discontinuation of anaesthesia to eye-opening (11 +/- 6 min), to response to commands (12 +/- 6 min), and to return of full wakefulness (21 +/- 10 min) after propofol/N2O were similar to those after propofol/O2, but significantly less (by approximately 30%) than those after halothane (P < 0.05). The overall incidence of emesis after propofol/N2O (53%) was greater than that after propofol/O2 (17%, P < 0.05) and comparable to that after halothane/N2O (58%). These data suggest that N2O has little effect on the rate of recovery after propofol, but significantly increases the incidence of postoperative emesis, thereby attenuating one of the main attributes of propofol anaesthesia.
    Pediatric Anesthesia 01/1998; 8(1):49-54. · 2.44 Impact Factor
  • Survey of Anesthesiology 01/1998; 42(6).
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    ABSTRACT: To investigate the efficacy of a subhypnotic dose of propofol to treat vomiting in children after adenotonsillectomy. Two hundred and fifty-two children, aged 2-12 yr, underwent a standardized anaesthetic opioid administration, and postoperative care after adenotonsillectomy, adenoidectomy or tonsillectomy. A prospective, double-blinded, placebo-controlled study was performed in 70 of the patients who retched or vomited after surgery and who had intravenous access. Patients were assigned randomly to receive either 0.2 mg.kg-1) propofol (n = 35), or placebo (intralipid 10%, n = 35). The overall incidence of vomiting during the first 18-24 hr was 50%. Of those who had received propofol after the first episode of vomiting, 63% relapsed requiring a rescue antiemetic compared with 57% of those who had received intralipid (P = NS). Of the children who received propofol, 54% experienced pain on injection and 46% were mildly sedated compared with 3% and 11%, respectively, in the placebo group (P < 0.003). We conclude that an intravenous bolus of 0.2 mg.kg-1 propofolis not effective in the treatment of postoperative vomiting in children after adenotonsillectomy when a standardized anaesthetic with thiopentone, halothane, nitrous oxide, and 1.5 mg.kg-1 codeine phosphate is used, but it does cause sedation and pain on injection.
    Canadian Journal of Anaesthesia 05/1997; 44(4):401-4. · 2.13 Impact Factor
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    ABSTRACT: Improvements in anaesthesia have led to the introduction of rapid-acting agents which quicken recovery and decrease sleepiness. Whether parents believe a rapid postanaesthetic recovery is an advantage is unknown. Therefore, we evaluated the parental perceptions, expectations and preferences for the postanaesthetic recovery of children. One hundred and three parents of children having ambulatory surgery completed a structured questionnaire and the results of 101 are presented. Results indicate that 93% of parents expect their child to be sleepy after surgery. Seventy-four per cent of parents indicated they would prefer their child to be sleepy or tired in the first 24 h postoperatively. Eight-five percent of parents would not be upset if their child's discharge was delayed up to three hours because their child was too sleepy. Finally 45.5% of parents are extremely concerned about their child experiencing postoperative pain and 68% believe that their child would be in more pain if they recovered rapidly from the anaesthetic. These results indicate that rapid recovery from anaesthesia and quick discharge from hospital are not key expectations of parents of children admitted for day surgery. Parents associate a rapid recovery with more pain. Parents need to be more fully informed of the advantages of a rapid recovery and reassured that children can recover quickly and completely but at the same time be comfortable postanaesthetic.
    Pediatric Anesthesia 02/1997; 7(2):139 - 142. · 2.44 Impact Factor
  • N Sikich, A S Carr, J Lerman
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    ABSTRACT: Improvements in anaesthesia have led to the introduction of rapid-acting agents which quicken recovery and decrease sleepiness. Whether parents believe a rapid postanaesthetic recovery is an advantage is unknown. Therefore, we evaluated the parental perceptions, expectations and preferences for the postanaesthetic recovery of children. One hundred and three parents of children having ambulatory surgery completed a structured questionnaire and the results of 101 are presented. Results indicate that 93% of parents expect their child to be sleepy after surgery. Seventy-four per cent of parents indicated they would prefer their child to be sleepy or tired in the first 24 h postoperatively. Eight-five percent of parents would not be upset if their child's discharge was delayed up to three hours because their child was too sleepy. Finally 45.5% of parents are extremely concerned about their child experiencing postoperative pain and 68% believe that their child would be in more pain if they recovered rapidly from the anaesthetic. These results indicate that rapid recovery from anaesthesia and quick discharge from hospital are not key expectations of parents of children admitted for day surgery. Parents associate a rapid recovery with more pain. Parents need to be more fully informed of the advantages of a rapid recovery and reassured that children can recover quickly and completely but at the same time be comfortable postanaesthetic.
    Pediatric Anesthesia 02/1997; 7(2):139-42. · 2.44 Impact Factor

Publication Stats

896 Citations
153.32 Total Impact Points

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Institutions

  • 1992–2007
    • SickKids
      Toronto, Ontario, Canada
  • 1992–2005
    • University of Toronto
      • Department of Anesthesia
      Toronto, Ontario, Canada
  • 2004
    • St. Michael's Hospital
      Toronto, Ontario, Canada
  • 1997
    • Waikato Hospital
      Hamilton City, Waikato, New Zealand