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| Introduction |
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The Richard Knill Award is presented by the Canadian Anesthesiologists' Society for the best scientific presentation by a member of the Society. The Richard Knill competition was instituted in memory of Dr. Richard Knill, a foremost researcher in anesthesiology and prominent collaborator to the Canadian Journal of Anesthesia (CJA).
The Annual Meeting Committee selects the top abstracts submitted for presentation by members of the Society at the Annual Meeting. The authors are invited to present their results at the Richard Knill competition. Presentations are marked by a jury composed of the members of the Editorial Board of the CJA.
In 2004, the Richard Knill Award was presented to Dr. David C. Campbell for his work on Patient Controlled Epidural Analgesia during labour.
The residents' competition brings together the scientific achievements of residents in the specialty. The Annual Meeting Committee selects the top abstracts submitted for presentation by residents at the Annual Meeting. The authors are invited to present their results at the Residents' Competition. Presentations are marked and ranked by a jury composed of representatives of Canadian Universities' Departments of Anesthesiology. A prize is awarded for first, second and third place.
In 2004, the first prize was awarded to Dr. Tejinder S. Chhina from the University of Toronto while the second and third prizes went to Dr. Kong E. You-Ten and Dr. Richard Brull, respectively, also from the University of Toronto.
All abstracts are published as submitted by the authors at the time of the Annual Meeting.
| RCT COMPARING PCEA vs PCEA + CIEA ON LABOUR OUTCOME |
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Institution Affiliation: Department of Anesthesia, Royal University Hospital, College of Medicine, University of Saskatchewan, 103 Hospital Drive, Saskatoon, SK, S7N 0W8
Richard Knill Award
INTRODUCTION: Patient controlled epidural analgesia (PCEA) delivery systems permits labouring women to determine the amount and timing of epidural analgesic medication for labour pain relief. Although PCEA reduces the amount of epidural medication received by labouring women compared to continuous infusion epidural analgesia (CIEA) (1,2), there have been no studies of sufficient size to detect differences in obstetrical outcomes when PCEA alone is compared to PCEA + CIEA. Importantly, the impact of PCEA + CIEA on the outcome of labour has yet to be properly evaluated using ambulatory epidural analgesics (3). Therefore, the purpose of this prospective, randomized, double-blinded study was to compare the impact of PCEA vs PCEA + CIEA, using ambulatory labour analgesia, on the incidence of cesarean delivery (C-D) and instrumented (forcep or vacuum) vaginal delivery (IVD).
METHODS: This study was conducted between Jan 2000 and Dec 2003. Following IRB approval and written informed consent, 300 nulliparous women undergoing induced labour, determined to be in established labour, <6 cm dilated and requesting labour epidural analgesia (LEA) were randomized. LEA was established with 20 ml of 0.8% Ropiv + 2 µg/ml Fent (3), with each woman then randomized to receive this same analgesic solution either via PCEA (5 ml bolus; 10 min lockout, No 4 hour limit) alone or PCEA (5 ml bolus; 10 min lockout, No 4 hour limit) plus CIEA (10 ml/hr) in a double-blind manner to maintain LEA. LEA and obstetric management were predetermined using strict protocols. Data was analyzed using an intent-to-treat model, major protocol violations (MPV) excluded. Data analysis included 2-tailed T test with P<0.05 considered significant.
RESULTS: 150 women were randomized in each group with no statistical differences in demographics, method of labour induction, cervical dilatation at time of LEA, gestational age, VAS pain scores prior to LEA and neonatal weight. Several MPV were identified in each group including 9 PCEA (1 "wet tap"; 8 epidural catheter replacements) and 6 PCEA + CIEA (1 "wet tap"; 3 epidural catheter replacements; 1 undiagnosed breech in 2nd stage; 1 PCEA pump programmed incorrectly). Therefore, the treatment allocations were administered to 141 women in the PCEA group and 144 women in the PCEA + CIEA group. Women in the PCEA group received significantly less epidural Ropiv (45.2 + 34.1 mg) compared to PCEA + CIEA (78.6 + 39.9 mg) P<0.0001. There were no statistical differences in the duration (min) of the 1st stage of labour with PCEA (414 + 249) and PCEA + CIEA (455 + 254) and 2nd stage with PCEA (127 + 86) and PCEA + CIEA (144 + 114) or incidence of C-D with 37 PCEA (26.2%) and 37 PCEA + CIEA (25.7%), IVD with 43 PCEA (30.5%) and 48 PCEA + CIEA (33.3%), or neonatal pH <7.20 and APGARS <7.
DISCUSSION: LEA using 0.08% Ropiv + 2 µg/ml Fent delivered by PCEA alone and PCEA + CIEA (10 ml/hr), provides effective analgesia throughout labour. Although, PCEA alone significantly reduces the amount of ambulatory epidural medication parturients receive during labour, our investigation did not identify any benefit to utilizing PCEA alone with regard to labour or neonatal outcome.
REFERENCES:
3 Anesth Analg 90: 13849, 2000
| EFFICACY OF PCEA VS PCEA + CIEA FOR AMBULATORY LABOUR ANALGESIA |
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Institution Affiliation: Department of Anesthesia, Royal University Hospital, College of Medicine, University of Saskatchewan, 103 Hospital Drive, Saskatoon, SK, S7N 0W8
Richard Knill Award
INTRODUCTION: The utilization of patient controlled epidural analgesia (PCEA) delivery systems for labour reduces the amount of epidural medication (1,2) and need for anesthesiologistdelivered supplemental analgesia (1,3) compared to continuous infusion epidural analgesia (CIEA). To date, no studies have evaluated the efficacy of ambulatory labour analgesia (4) nor need for Anesthesiologist-administered "top ups" when PCEA alone is compared to PCEA + CIEA. Therefore, the purpose of this prospective, randomized, double-blinded study was to compare the impact of PCEA vs PCEA + CIEA on labour analgesic efficacy and need for Anesthesiologistadministered "top ups".
METHODS: This study was conducted between Jan 2000 and Dec 2003. Following IRB approval and written informed consent, 300 nulliparous women undergoing induced labour, determined to be in established labour, <6 cm dilated and requesting labour epidural analgesia (LEA) were randomized. LEA was established with 20 ml of 0.8% Ropiv + 2 µg/ml Fent (4), with each woman then randomized to receive this same analgesic solution either via PCEA alone (5 ml bolus; 10 min lockout, No 4 hour limit) alone or PCEA (5 ml bolus; 10 min lockout, No 4 hour limit) plus CIEA (10 ml/hr) in a double-blind manner to maintain LEA. LEA and obstetric management were predetermined using strict protocols. An "a priori" decision was made to analyze only the data for a vaginal delivery to eliminate the potential impact of "dystocia" which has a higher analgesic requirement. Data analysis included 2-tailed unpaired T-test and Chi square with P<0.05 considered significant.
RESULTS: 211 women of the 300 randomized, 104 (73.8%) PCEA alone and 107 (73.6%) PCEA + CIEA delivered vaginally and were included in the analysis. There were no statistical differences in demographics, method of labour induction, cervical dilation at time of LEA initiation, gestational age, VAS pain scores prior to LEA and 30 min post LEA initiation and neonatal weight. 3 PCEA (2.8%) withdrew due to inadequate analgesia and 1 PCEA + CIEA (0.9%) withdrew. VAS Pain scores were significantly higher (P<0.02) at each cervical dilation between 310 cm in PCEA vs PCEA + CIEA (Figure 1
). Significantly more women required Anesthesiologist-administered supplemental "top ups" with 43 PCEA (41.3%) requiring a total of 64 "top ups" and 29 PCEA + CIEA (27.1%) requiring a total of 45 "top ups" (P<0.03). Mean postpartum analgesic satisfaction was significantly greater at 2 hrs with PCEA + CIEA (90.3 + 12.6) vs PCEA (84.2 + 20.9) and 24 hrs with PCEA + CIEA (90.6 + 10.9) vs PCEA (84.7 + 21.1), both P<0.02.
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REFERENCES:
4 Anesth Analg 90: 13849, 2000
| METOPROLOL AFTER VASCULAR SURGERY (MAVS) |
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Institution Affiliation: Dept of Anesthesia McMaster University, University of Western Ontario, & Queens University H Yang, University of Ottawa, B309, 1053 Carling Ave, Ottawa. K1Y 4E9
Richard Knill Award
INTRODUCTION: In vascular surgery, ß-blockers are increasingly used to prevent peri-operative cardiac complications. This is a report of a RCT on the peri-operative use of metoprolol.
METHODS: After REB approval, patients undergoing abdominal aortic surgery, infra-inguinal or extraanatomical revascularization were recruited to a double-blind RCT of peri-operative metoprolol versus placebo. Consenting eligible patients were randomized to either IV/oral metoprolol or placebo 2 hours pre-op. Study medication was continued IV q6h or po bid until hospital discharge or maximum 5 days post-op. The primary outcome on an intent-to-treat basis was the 30-day post-op composite incidence of non-fatal MI; unstable angina; new CHF; new atrial or ventricular dysrhythmia requiring treatment; or cardiac death.
RESULTS: 497 patients consented and were randomized: 247 metoprolol and 250 placebo. The groups were balanced in demographics and pre-op co-morbidities. Early study drug discontinuation was 12% in placebo and 13% in metoprolol patients. One or more events in the primary outcome cluster occurred in 30 (12.0%) placebo and 25 (10.1%) metoprolol patients. The risk difference, 1.9% (CI 7.6% to 4.0%), was not significant (p=0.40). The observed effects in the primary cluster are shown (Table
). Intra-operatively, more metoprolol patients had bradycardia requiring treatment (53/247 vs 19/250, p=0.00001) and hypotension requiring treatment (26/250 vs 84/247, p=0.0046).
DISCUSSION: This is the largest peri-operative $-blocker RCT completed to-date. An unblinded study 1 on 112 patients found a 10-fold reduction in MI and cardiac mortality. Our study was double-blinded and our patients were considered moderate/high risk. Another study reported 1732% cardiovascular event rate2. It was under-powered to detect 30-day treatment effects although an effect beyond 6 months was noted. Our event rate was lower than previous reports, decreasing the studys calculated power to detect 50% RRR from 80% to about 40%. In summary, our preliminary 30-day results did not support a clinically useful metoprolol effect in reducing the cardiac event rate in these vascular patients. The 6-month and longer-term follow-ups have yet to be completed.
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Reference List
1 Poldermans D, Boersma E, Bax JJ, Thomson IR, van de Ven LL, Blankensteijn JD et al. The effect of bisoprolol on perioperative mortality and myocardial infarction in high-risk patients undergoing vascular surgery. Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography Study Group. N Engl J Med 1999;341[24]: 178994.
2 Mangano DT, Layug EL, Wallace A, Tateo I. Effect of atenolol on mortality and cardiovascular morbidity after noncardiac surgery. Multicenter Study of Perioperative Ischemia Research Group. N Engl J Med 1996; 335(23):171320.
| IN CARDIAC SURGERY, BLOOD VOLUME ACCOUNTS FOR THE INCREASED RISK IN WOMEN |
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Institution Affiliation: Toronto General Hospital, University Health Network, University of Toronto 200 Elizabeth Street, Toronto, Ontario M5G 2C4
Richard Knill Award
BACKGROUND: The risk of death after cardiac surgery is higher in women than in men. The reason for this difference is still unclear. It has been known that women have a substantially smaller circulation blood volume (CBV) than men, which means that they become more anemic during surgery and receive red blood cell (RBC) transfusions more often. The objective of this study was to determine if these two variables account for the increased risk of death in women after cardiac surgery with CPB.
METHODS: After REB approval, data were prospectively collected on consecutive patients undergoing cardiac surgery with CPB from 1999 to 2003 in an academic hospital. Two multivariable logistic regression models were constructed to determine the independent predictors of in-hospital, all-cause mortality. Model 1 mimicked previous studies and assessed the relationship between gender and mortality by adjusting for multiple peri-operative variables excluding those related to intraoperative anemia and RBC transfusion. Model 2 included the latter variables (measured as nadir hematocrit during CPB (nHct) and transfusion of = 2 units of RBCs on the day of surgery) as well as the variables included in model 1. The relationships between gender and mortality in these models were examined.
RESULTS: Of the 9215 patients who underwent cardiac surgery with CPB, 169 (1.8%) died. The unadjusted risk of death was higher in women than men [68/2316 (2.9%) vs. 101/6899 (1.5%); P<0.0001 (chi-squared test)]. Compared to men, women were more anemic during surgery [mean nHct 20% vs. 24%; P<0.0001 (t-test)] and received = 2 units of RBCs more often [52% vs. 22%; P<0.0001 (chi-squared test)]. In model 1, gender was independently related to risk of death, with the odds of death 1.6 times higher in women (95% C.I. 1.1 2.3; P=0.015). In model 2, however, gender was no longer independently related to risk of death (P=0.2); it was replaced by nHct (P=0.01) and RBC transfusion (P=0.001).
CONCLUSION: Female gender is not independent risk factor for death during cardiac surgery with CPB when factors related to perioperative anemia and RBC transfusion are adjusted for. The increased risk of death in women, therefore, is due to their smaller CBV.
| ANEMIA INCEASES RAT CEREBRAL CORTICAL nNOS PROTEIN LEVELS |
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Institution Affiliation: University of Toronto, St. Michaels Hospital, 30 Bond Street, Toronto, Ontario M5B 1W8.
Richard Knill Award
INTRODUCTION: Increased cerebral cortical neuronal nitric oxide synthase (nNOS) expression has been identified following exposure to hypoxic environmental conditions (1) and may mediate the associated compensatory increase in cerebral blood flow (CBF) observed during hypoxia (2). As such, nNOS may contribute to neuroprotective mechanisms directed at optimizing CBF during hypoxia. The current study tests the hypothesis that acute hemodilutional anemia causes cerebral hypoxia triggering an increase in cerebral nNOS protein levels at clinically relevant hemoglobin concentrations.
METHODS: With Animal Care Committee approval, anesthetized rats underwent tail artery and vein cannulation to monitor arterial pressure and performing hemodilution. Hemodilutional anemia was achieved by exchanging 30 ml.kg-1 of blood with pentastarch over 10 minutes. Hemoglobin concentrations were assessed by co-oximetry. Control animals were not hemodiluted. Animals exposed to hypoxia (10% oxygen) served as positive controls. Rats were recovered for 6,12, 24, 48 hours, 4 and 7 days (n=6 rats/group/time). Cerebral cortical nNOS levels were assessed by Western blot analysis. Band density was quantified digitally and reported as pixels.µg protein-1. A two-way ANOVA and post hoc Tukey test were used to assess data. Significance was assigned at p < 0.05 (Mean ± SD).
RESULTS: The hemoglobin concentration in anemic rats decreased to 64 ± 11 g.L1 following hemodilution (p<0.05) and then increased toward control values by 7 days. At 12 hours, there was a significant increase in cerebral cortical nNOS protein in both anemic (1,847 ± 195) and hypoxic rats (2,145 ± 138), relative to controls (1121 ± 295) (p<0.05). At 24 hours, nNOS protein remained significantly elevated in hypoxic rats but returned toward control values in anemic rats (1,643 ± 302).
DISCUSSION: Acute hemodilutional anemia caused a transient increase in cerebral cortical nNOS protein, which diminished as the hemoglobin concentration recovered toward control values. Hypoxia produced a more sustained increase in nNOS, supporting the hypothesis that hypoxia may have triggered the increase in nNOS observed in anemic rats. Increased nNOS may contribute to endogenous cerebral neuroprotective mechanisms invoked to protect the brain during anemia. (CAS, PSI Support).
REFERENCES:
1) Adv Exp Med Biol 454:319, 1998.[Medline]
2) J Cereb Blood Flow Metab 20: 220, 2000.[Medline]
| IMPACT OF FAST-TRACKING ON RECOVERY TIME AND NURSING WORKLOAD |
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Institution Affiliation: Department of Anesthesia, Toronto Western Hospital, University of Toronto, 399 Bathurst Street, Toronto M5T 2S8
Richard Knill Award
INTRODUCTION: Bypassing the post anesthesia care unit (PACU) may decrease recovery time after ambulatory surgery and may result in cost savings from a reduced nursing workload. This prospective randomized study evaluated the effects of bypassing PACU on patient recovery time, nursing workload and costs.
METHODS: After obtaining institutional ethics committee approval, 207 adult patients undergoing hysteroscopy, arthroscopy or gynecological laparoscopy were enrolled in this study. Anesthesia was induced with propofol and fentanyl and maintained with desflurane or sevoflurane. All patients received analgesic and anti-emetic prophylaxis. The electroencephalographic bispectral index values were maintained at 4060 intraoperatively. On completion of the procedure, patients were randomized to either fast-tracking or routine recovery group. Patients in the fasttracking group were transferred directly to the ambulatory surgery unit (ASU) when they achieved a fast-tracking score of = 12 1 within 10 minutes. All other patients were transferred to PACU prior to the ASU. Postoperative nursing workload was recorded using a Patient Care Hour (PCH) chart, based on the type and frequency of nursing interventions in the PACU and ASU. A cost associated with this nursing workload was calculated. Postoperative pain, nausea, overall patient satisfaction and time to discharge home was also recorded.
RESULTS:
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DISCUSSION: Bypassing PACU significantly decreased the patients recovery time in hospital without increasing postoperative side-effects or compromising patient satisfaction. However, the nursing workload and the associated cost were not significantly affected.
REFERENCES
(1) White PF, Song D. New criteria for fast-tracking after outpatient anesthesia: a comparison with the modified Aldretes scoring system. Anesth Analg 1999; 88: 106972.
| EFFECT OF RECOMBINANT FACTOR VIIA ON RABBIT VASCULAR GRAFT PATENCY |
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Institution Affiliation: Departments of Anesthesia, Surgery and Medicine, St. Michaels Hospital, University of Toronto, Toronto, ON, M5B 1W8
Outstanding Resident 1st. Prize
INTRODUCTION:
Cardiovascular surgery is still associated with significant morbidity and mortality due to bleeding. Several case reports have suggested that a new agent, recombinant Factor VIIa (rVIIa), may reduce bleeding in patients failing conventional treatment (1; 2). The purpose of this study was to determine if adding rVIIa to the already thrombogenic environment of new vascular anastomoses could result in higher incidence of graft occlusion.
METHODS:
With Animal Care Committee approval, 19 rabbits were anesthesized with ketamine (10mg/kg), xylazine (2mg/kg), and 12% isoflurane in 100% oxygen. Through a midline neck incision, the right jugular and both carotid arteries were exposed. The animals were anticoagulated with heparin, and a 23 cm section of right jugular vein was then excised and grafted to the right carotid artery with two end to side anastomoses. The left carotid artery was ligated and re-anastomosed in an end to end fashion. Following protamine administration the grafts were inspected before skin closure to ensure adequate flow. Animals then received either placebo or 300ug/kg of rVIIa intravenously. An ultrasound was performed at 3 hours and 24 hours to assess graft flow, and the presence of occlusive clot. On sacrifice, the grafts were visually inspected for thrombus. The primary outcome was ultrasound evidence of no flow or presence of occlusive thrombus in the graft. Data was analyzed using ANOVA, chi-square or fishers exact test where appropriate, with p<0.05 considered significant.
RESULTS:
Three animals were excluded for technical reasons. rVIIa treated animals had a significantly higher incidence of graft occlusion (vein 7/8 vs 1/8, p=0.01; artery 7/8 vs 2/8, p<0.05) and lower average vein graft flow (26.7 +/ 15.34 vs 5.5 +/ 13.47 ml/min, p<0.05) . There was no significant difference between the two groups in graft diameter, physiological variables, hemodynamics or anticoagulation.
DISCUSSION:
This study suggests that high dose rVIIa (300ug/kg) leads to an increased incidence of fresh vascular graft thrombosis. It is still unknown if these results would be obtained with lower doses. Our findings may guide further research and clinical use of rVIIa
REFERENCES
(1) Can J Anaesth 2003; 50(6): 599
(2) Anesth Analg 2001; 93(2): 287
| SUB-MAC CONCENTRATIONS OF ISOFLURANE TARGET NOVEL MURINE GABAARs |
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Institution Affiliation: Departments of aAnesthesia, Sunnybrook & Womens College Health Sciences Centre, bPhysiology, cInstitute of Medical Sciences, and d Pharmaceutical Sciences, University of Toronto, Toronto, Ontario, Canada
Outstanding Resident 2nd. Prize
INTRODUCTION
Sub-anesthetic concentrations of propofol, midazolam and volatile anesthetics produce amnesia without causing sedation, immobility and unconsciousness.12 The mechanisms by which sub-anesthetic concentrations produce amnesia are unknown. It is believed that enhancement of inhibitory current mediated by synaptic GABAA receptors (GABAARs) is the predominant mechanism of action of most anesthetics. Our laboratory showed that an extrasynaptic tonic inhibitory conductance in hippocampal neurons is sensitive to low concentrations of intravenous anesthetics3 . Here, we test the hypothesis that the tonic inhibitory conductance is highly sensitive to volatile anesthetics due to the unique subunit composition of the underlying GABAARs.
METHODS
Animal protocols were approved by the University of Toronto Animal Care Committee. Whole-cell currents were recorded from HEK 293 cells transfected with human GABAARs cDNA (
1ß3
2L or
5ß3
2L), and from cultured hippocampal neurons obtained from wild-type and genetically modified mice lacking the
5-subunit of the GABAARs (
5-/- knock-out mice). Data are expressed as mean ± SEM and p<0.05 was considered significant.
RESULTS
Sub-MAC concentrations of isoflurane (25 µM; 0.1 MAC) reversibly enhanced the tonic current (166 ± 24.9%, n = 10, p < 0.01). Moreover, results from transfected HEK 293 cells and hippocampal neurons of
5-/- knock-out mice indicate that isoflurane enhanced the tonic conductance by selectively targeting GABAARs containing the
5 subunit.
DISCUSSION
Volatile anesthetics can cause amnesia at concentrations well below those required to cause sedation, unconsciousness and immobility. These results suggest that volatile anesthetics induce the amnestic effects through enhancement of the tonic current in hippocampal neurons by targeting
5-containing GABAARs. Our data also implicate the
5-containing GABAARs as playing a critical role in learning and memory processes4.
REFERENCES
| REGIONAL ANESTHESIA VS GENERAL ANESTHESIA FOR AMBULATORY HAND SURGERY |
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, Dimitri Anastakis MD MED FRCSC FACS
, and Herbert von Schroeder MD MSC FRCSC
Institution Affiliation: *Regional Anesthesia and
Hand Surgery programs, Toronto Western Hospital, University Health Network, 399 Bathurst Street, Toronto, Ontario, Canada M5T 2S8
Outstanding Resident 3rd. Prize
INTRODUCTION: Regional anesthesia (RA) is associated with superior analgesia and fewer adverse effects compared to general anesthesia (GA) during in-hospital recovery after ambulatory hand surgery [1], but longer duration of benefit is unknown. This study investigates whether RA or GA provides superior analgesia with fewest adverse effects up to two weeks following ambulatory hand surgery.
METHODS: After IRB approval and informed consent, 100 patients undergoing ambulatory hand surgery were randomized to RA (n=50) or GA (n=50). RA comprised of axillary brachial plexus block using 1.5% lidocaine with epinephrine. GA included fentanyl, propofol, and desflurane. All patients received ketorolac. Fentanyl and oral opioid preparations were administered postoperatively as needed. Preoperatively, all patients rated their hand pain (Visual Analog Scale;VAS) and pain-related disability (Pain-Disability Index[2];PDI). Postoperatively, eligibility for bypassing PACU ("fast-track") was determined (Modified Aldrete score[3]), and pain (VAS) and home-readiness scores (Postanesthesia Discharge Scoring System[4]) were recorded. On postoperative days (POD) 1, 7, and 14, patients documented pain (VAS), opioid consumption, nausea/vomiting, weakness and paresthesia in the operative extremity, and satisfaction (VAS). Patients repeated the PDI on POD 14. Intention-to-treat analysis was undertaken by t-test, Mann-Whitney U, or
2 with p<0.05 considered significant.
RESULTS: Demographics, medical history, preoperative pain and PDI, and procedure types were similar. More RA patients were fast-track eligible (p<0.001), while duration of stay in PACU was shorter in the RA group (p<0.001). During in-hospital recovery, the time to first analgesic requirement was longer in the RA group (p<0.001), and fentanyl consumption (p<0.001), oral morphine equivalent consumption (p<0.001), and pain (fig.1
) were lower in the RA group. More GA patients suffered nausea/vomiting during in-hospital recovery (p<0.05). RA patients achieved home-readiness earlier (p<0.001). On POD 1, 7, and 14, there were no differences in pain (fig.1
), opioid consumption, nausea/vomiting, weakness, paresthesia, or satisfaction. There was no difference in PDI on POD 14.
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REFERENCES:
(2) Arch Phys Med Rehabil 68:43841.
(3) J Perianesth Nurs 13:14855.
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| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |