| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
* From the Department of Anesthesia and Perioperative Medicine, and the
Department of Physiology and Pharmacology, London Health Sciences Centre, University of Western Ontario, for the Evidence-Based Perioperative Clinical Outcomes Research (EPiCOR) Group, London, Ontario, Canada.
Address correspondence to: Dr. Davy C. Cheng, Department of Anesthesia and Perioperative Medicine, London Health Sciences Centre - University campus, 339 Windermere road, Room 3-CA19, London, Ontario N6A 5A5, Canada. Phone: 519-663-3031; Fax: 519-663-3161; E-mail: davy.cheng{at}lhsc.on.ca
 |
Abstract |
|---|
 TOP Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
Methods: A comprehensive search was undertaken to identify all randomized controlled trials of PCA vs NCA. Medline, Cochrane Library, Embase, and conference abstract databases were searched from the date of their inception to August 2005. The primary postoperative outcome was defined as mean visual analogue scale (VAS) scores. Secondary postoperative outcomes included cumulative morphine equivalents, intensive care unit (ICU) and hospital length of stay, postoperative nausea and vomiting, sedation, respiratory depression, and all-cause mortality. Odds ratios or weighted mean differences (WMD) and their 95% confidence intervals (CI) were calculated for discrete and continuous outcomes, respectively.
Results: Ten randomized trials involving 666 patients were included. Compared to NCA, PCA significantly reduced VAS at 48 hr (WMD –0.73, 95% CI –1.19, –0.27), but not at 24 hr (WMD –0.19, 95% CI –0.61, 0.24). Cumulative morphine equivalents consumed were significantly increased at 24 hr (WMD 6.84 mg, 95% CI 0.97, 12.72 mg), and at 48 hr (WMD 10.46 mg 95% CI 2.02, 18.9 mg) for PCA compared with NCA. Ventilation times, length of ICU stay, length of hospital stay, patient satisfaction scores, sedation scores, and incidence of postoperative nausea and vomiting, respiratory depression, severe pain, discontinuations, and death were not significantly different between groups, but these outcomes were generally under-reported.
Conclusions: In postcardiac surgical patients, PCA increases cumulative 24 and 48 hr morphine consumption, and improves 48-hr VAS compared with NCA.
|
Introduction |
|---|
|
TOPAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
A number of randomized trials have been published that evaluate the relative efficacy and safety of PCA vs nurse-controlled analgesia (NCA) in cardiac surgical patients. However, these trials have had insufficient power to adequately explore clinically important effects. Presently, no meta-analysis has been published in this area. Appropriate combination of randomized trials through meta-analysis would increase the power to evaluate whether significant differences in efficacy and safety exist between PCA and NCA. We sought to determine, through systematic review with meta-analysis, whether PCA reduces VAS pain scores, morbidity, and resource utilization when compared with NCA.
|
Methods |
|---|
|
TOPAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Inclusion criteria
Studies were included if they met each of the following: 1) randomized allocation to PCA vs NCA; 2) adult patients undergoing coronary artery bypass surgery or valvular repair; and 3) reporting at least one pertinent clinical or economic outcome.
Data extraction
Two authors independently identified trials for inclusion and extracted information on demographics, interventions, and outcomes. Two reviewers independently assigned each trial a Jadad quality score that evaluates randomization, blinding, and completeness of follow-up (maximum score, 5).6 Disagreements were resolved by consensus.
Endpoints
The primary postoperative outcome was defined as mean VAS. Secondary clinical outcomes included postoperative nausea and vomiting, severe sedation, respiratory depression, severe pain, pruritis, constipation, pulmonary complications, hypotension, patient dropouts, patient satisfaction, and all-cause mortality. Economic outcomes included intensive care unit (ICU) length of stay, hospital length of stay, and hospital costs. Visual analogue scores represent a 10-cm scale from 0 to 10, where 0 represents no pain and 10 represents worst imaginable pain. When mean VAS scores were provided graphically, the values for the mean and standard deviation were derived by interpolation when possible. Visual analogue score at 24 hr was defined as the mean VAS over the first 24 hr post-operation. Visual analogue score at 48 hr was defined as the mean VAS during the interval of 24 to 48 hr postoperation. If the mean VAS was not available for the 24- or 48-hr timeframe, the VAS for the time period closest to 24 or 48 hr was used. Ventilation time was measured from end of surgery to time of tracheal extubation. Intensive care and hospital length of stay were measured from end of surgery to ICU or hospital discharge, respectively. Nausea and vomiting was defined as the presence of nausea and/or vomiting at any time point after surgery. Patient discontinuations were defined as patients discontinuing the study, for any reason, after randomization to treatment with PCA or NCA. Patient satisfaction scores were defined as per the study authors. Severe sedation was defined as difficulty in arousing a patient or unconsciousness. Patient satisfaction was defined by the authors, and included patients rating their treatment as "good" or "very good" on verbal or written questionnaires administered in hospital. Morphine sulphate consumption was calculated by converting narcotic doses into morphine equivalents according to the authors definitions or according to accepted equivalents (1 mg piritramide = 1 mg morphine sulphate, 1 mg ketobemidone = 1 mg morphine sulphate).
Statistical analysis
Outcomes were analyzed as dichotomous variables, with the exception of VAS, cumulative morphine equivalents, patient satisfaction scores, sedation scores, ventilation time and length of stay which were analyzed as continuous variables when means and standard deviation were reported. For dichotomous variables, odds ratios (OR) and 95% confidence intervals (CI) (OR, 95% CI) were calculated. For continuous variables, the weighted mean difference (WMD; 95% CI) was calculated. If significant differences were found for proportions, it was planned to calculate the absolute risk reduction and number needed-to-treat.7 Heterogeneity was explored using the Q-statistic, with P < 0.10 suggesting significant heterogeneity between trials. In addition, the I-squared value was calculated to define the proportion of heterogeneity observed between trials that could be explained by chance. For each outcome, the Mantel-Haentzel (fixed effect) or DerSimonian and Laird (random effects) model was used when the Q-statistic suggested lack or presence of heterogeneity, respectively.
When possible, data extraction and analysis was by intention-to-treat. Sensitivity analysis was planned to explore the potential effect of trial quality, and patients excluded in non-intent-to-treat trials using a worst-case scenario assumption.
Publication bias was explored through visual inspection of funnel plots for each outcome, in which the inverse of the estimated variance of the natural logarithm of the adjusted relative risk was plotted against the natural logarithm of the adjusted relative risk for each disease.8 Statistical significance was defined as a two-tailed P < 0.05, or 95% CI that excluded values of no difference. Data were analyzed by use of Comprehensive MetaAnalysis® (Englewood, NJ, USA, 2002) and RevMan (v4.2, Cochrane Collaboration, 2004).
|
Results |
|---|
|
TOPAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
). The median Jadad score was 3 (range: 2–4).6 Most baseline characteristics were similar between groups; however, the NCA group was older and had a greater number of female patients. (Table II). Four trials evaluated patients undergoing coronary artery bypass surgery exclusively, while six trials evaluated patients undergoing both CABG and valvular surgery. Overall, 88% of included patients underwent CABG. Clear evidence of publication bias was not found for any endpoint, although lack of power limited evaluation in some cases. Significant heterogeneity across trials was found for 24 and 48-hr VAS, 24 and 48-hr morphine equivalents, patient satisfaction scores, number of patients experiencing nausea or vomiting, number of patients with severe pain, and number of patients satisfied.
|
|
outlines the results for clinical and economic outcomes. For the primary endpoint of mean VAS at 24 hr there was no difference between the PCA group and NCA group (WMD –0.19, 95% CI –0.61 to 0.24). However, mean VAS score was significantly reduced at 48 hr (WMD –0.73, 95% CI –1.19 to –0.27) in the PCA group compared with NCA, and cumulative morphine equivalent consumption was significantly increased at both 24 hr (WMD 6.84 mg, 95% CI 0.97 to 12.72 mg), and 48 hr (WMD 10.46 mg 95% CI 2.02, 18.9 mg). No significant differences were found for resource utilization outcomes including ICU length of stay (WMD 0.05 days, 95% CI –0.19 to 0.29), and hospital length of stay (WMD –0.27 days, 95% CI –0.81 to 0.27), and costs were not reported in any study. Similarly, no significant difference was found for nausea and vomiting (OR 0.93, 95% CI 0.36 to 2.4), severe sedation (OR 0.83, 95% CI 0.29 to 2.35), respiratory depression (OR 1.4, 95% CI 0.39 to 5.08), severe pain (OR 0.71, 95% CI 0.18 to 2.90), patient discontinuations (OR 0.74, 95% CI 0.36 to 1.5), patient satisfaction (OR 3.32, 95% CI 0.57 to 19.48), and all-cause mortality (OR 1.45, 95% CI 0.17 to 12.08). Patient satisfaction scores and sedation scores did not differ significantly between groups (Figures 1–15, available as Additional Material at www.cja-jca.org). No studies reported on the following outcomes: pruritus, constipation, pulmonary complications, and hypotension. Sensitivity analyses by study quality were not possible since the studies had similar quality scores, and worst-case scenario sensitivity analysis was not possible due to inadequate information on dropouts.
|
|
Discussion |
|---|
|
TOPAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
In the real world setting, the potential differences in narcotic utilization and resulting pain relief between NCA and PCA might be even greater than suggested by this analysis, given that the increased attention paid to the NCA group as a direct result of being observed in a randomized controlled trial (Hawthorne effect) may have predisposed the results toward more conservative differences in narcotic utilization between PCA and NCA. The lack of differences observed between NCA and PCA within the first 24 hr postoperatively may be expected given that these patients traditionally have 1:1 or 1:2 nursing care which allows for effective pain management through nurse administered narcotics, with less chance for differential treatment between groups during this time period.
Significant heterogeneity was present for cumulative morphine equivalents at 24 and 48 hr and for VAS at both 24 and 48 hr. This is expected as the practice patterns for anesthesia and opioids given interoperatively were variable, and since differing opioids (with uncertainty of exact morphine equivalency) were used within the PCA regimen. In addition, some studies allowed concomitant prn or scheduled use of adjunctive non-steroidal anti-inflammatory agent (NSAID) analgesics or acetaminophen. Also, some of the heterogeneity in VAS may be attributable to the differing practices across institutions in measuring VAS, whether at rest, provoked by cough, or after movement.
Postoperative pain control in cardiac surgical patients has become increasingly important with the shift from high dose intraoperative narcotic being the standard, to more moderate doses becoming the norm to facilitate fast-track coronary bypass surgery.29 While reduced intraoperative narcotic facilitates early tracheal extubation and cost-savings, it has led to a concern about the potential for increased pain following surgery. Numerous pain management techniques have been examined to improve pain scores without prolonging intubation. In particular, NSAIDs have been studied to reduce postoperative pain and mitigate potential narcotic-induced side effects. While they seem effective in reducing total morphine consumption and VAS pain scores, NSAIDs also bring risks including renal dysfunction, sternal wound infection, and bleeding.30 Intrathecal morphine has been used preoperatively to treat postoperative pain. Doses have ranged widely and while some studies suggest no ventilatory depression other studies have suggested a risk of hypoventilation and delayed weaning.31–33 Thoracic epidurals have also been tried with good success; however, concerns over epidural hematomas have precluded their widespread acceptance.34,35
Unfortunately, incomplete reporting of adverse events prevented adequate analysis of risks associated with PCA use. Since the absolute increase in narcotic use in the PCA group was small (7 mg over 24 hr), it would be unexpected to find significant differences in narcotic-induced adverse effects between groups even with adequate reporting and/or trials of greater sample size.
Comparison with other surgical literature
There exist no other systematic reviews or meta-analyses of PCA vs NCA randomized trials in cardiac surgery. A previous systematic review of miscellaneous surgical patients included randomized studies of PCA vs NCA (iv, im, sc narcotics) and found improvements in VAS and patient satisfaction with PCA.2 There has been widespread adoption of PCA in the treatment of postoperative pain, as it not only improves patient comfort but also improves resource utilization.9,10 The disparate findings between this paper and previous studies may relate both to the type of surgery, degree of postoperative pain and timely administration of iv analgesia by nurses caring for patients in the ICU following cardiac surgery.
Strengths and limitations
The results of this analysis must be interpreted in light of the strengths and limitations of the included trials. The rigour of this analysis, as evidenced by comprehensive searches for randomized trials in any language and the adherence to QUOROM recommendations, suggests that this represents a complete summary of best available evidence.
It is important to note that the highly selected population found in these trials, which was generally younger and had fewer overall coronary vessel grafts than the national average in the United States36 may impact the generalizability of the findings. In addition, a number of the trials were performed in the early 1990s, suggesting the surgical and anesthetic techniques may be less relevant to predominant practice today. The prolonged ventilation time in the trials (nearly 12 hr in each group), and the prolonged ICU stay (over two days in each group) highlights the fact that most trials predated the fast-track era. A number of advances in anesthesia, including multimodal analgesia, have resulted in reduced pain postoperatively. Thus, any differences observed between PCA and NCA may be overpowered by recent advances.
Despite the fact that only randomized trials were included in this meta-analysis, both the number of females and age appear to be unevenly distributed between groups. Whether the excess number of females included in the NCA group compared with the PCA group impacted the results of this meta-analysis remains indeterminate. While there has been some empirical evidence of gender differences in perception of pain in other surgical trials,37 research in this area is very preliminary. That the preponderance of females in the NCA group, which may have biased results in favour of PCA, cannot be ruled out at this time. While patients in the NCA group were statistically significantly older, it is unlikely that clinically the 1.2 yr difference would have a large impact on the results.
The heterogeneity observed between trials is not unexpected; given the diverse anesthetic and surgical practice patterns and institutional protocols that would variably impact outcomes such as length of ventilation and length of stay. In addition, the intervals during which VAS was measured differed (i.e., some trials reported average VAS from 0–24 hr, while others reported average VAS from 12–24 hr) across studies, and it is not surprising that significant heterogeneity was found. Nevertheless, since our analysis examined the difference in VAS between groups, the differing definitions should not materially impact the overall conclusions.
Since few studies contributed data to the out-comes of interest related to narcotic adverse effects, this meta-analysis remained underpowered to detect clinical significant differences between PCA and NCA. Notwithstanding this lack of power, this meta-analysis represents the best state of knowledge for PCA in postcardiac patients. Future studies should focus on increasing the power to detect important differences in VAS in today’s context of fast-tracked cardiac surgery, and patient-reported outcomes such as satisfaction should be evaluated. Also, the relative risk of adverse events with PCA vs NCA, and the costs should be examined in future studies. The paucity of studies evaluating PCA in the contemporary surgical and anesthetic context is surprising given the widespread use of PCA worldwide. Clearly, sufficient eligible patients exist to allow for adequately powered studies.
While this analysis delineates the landscape of existing evidence, it also serves to highlight gaps that remain. Most notable is the lack of adequate numbers of randomized trials evaluating PCA compared with NCA that report on clinically relevant narcotic adverse effects. Also notable, is the lack of research on patient subgroups likely to benefit more from PCA, which may include younger patients, fast-tracked patients, and those with preexisting chronic narcotic use. Finally, valid economic analysis of PCA compared with NCA should be undertaken in order to determine whether the resource allocation required is worthy of the outcomes achieved.
Conclusions and implications
Overall, the use of PCA reduced 48-hr VAS scores by 25% (absolute VAS difference 0.7) while increasing narcotic cumulative consumption by approximately 7 mg at 24 hr. Whether this modest benefit is sufficient to warrant recommending PCA over NCA requires further understanding of patient preferences and cost-effectiveness. Future trials should focus on high-risk populations likely to require more intensive analgesic regimens, and should be adequately powered to evaluate the impact of PCA on narcotic-induced adverse effects and patient satisfaction. In addition, cost-effectiveness studies will be required to determine whether the routine use of PCA should be advocated in place of NCA in postcardiac surgical patients.
|
Acknowledgments |
|---|
|
Footnotes |
|---|
Presented in part at the Canadian Anesthesiologists’ Society Annual Meeting, Vancouver, June 2005, and at the Health Technology Assessment International Annual Meeting, Rome, June 2005.
Competing interests: None declared.
Accepted for publication October 31, 2005. Revision accepted November 30, 2005.
|
References |
|---|
|
TOPAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
2 Walder B, Schafer M, Henzi I, Tramer MR. Efficacy and safety of patient-controlled opioid analgesia for acute postoperative pain. A quantitative systematic review. Acta Anaesthesiol Scand 2001; 45: 795–804.[Medline]
3 Dolin SJ, Cashman JN, Bland JM. Effectiveness of acute postoperative pain management: I. Evidence from published data. Br J Anaesth 2002; 89: 409–23.
4 Cashman JN, Dolin SJ. Respiratory and haemodynamic effects of acute postoperative pain management: evidence from published data. Br J Anaesth 2004; 93: 212–23.
5 Moher D, Cook DJ, Eastwood S, Olkin I, Rennie D, Stroup DF. Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statement. Quality of Reporting of Meta-analyses. Lancet 1999; 354: 1896–900.[Medline]
6 Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 1996; 17: 1–12.[Medline]
7 Altman DG. Confidence intervals for the number needed to treat. BMJ 1998; 317: 1309–12.
8 Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315: 629–34.
9 D’Haese J, Vanlersberghe C, Umbrain V, Camu F. Pharmaco-economic evaluation of a disposable patient-controlled analgesia device and intramuscular analgesia in surgical patients. Eur J Anaesthesiol 1998; 15: 297–303.[Medline]
10 Chan VW, Chung F, McQuestion M, Gomez M. Impact of patient-controlled analgesia on required nursing time and duration of postoperative recovery. Reg Anesth 1995; 20: 506–14.[Medline]
11 Dal D, Kanbak M, Caglar M, Aypar U. A background infusion of morphine does not enhance postoperative analgesia after cardiac surgery. Can J Anesth 2003; 50: 476–9.
12 Bois S, Couture P, Boudreault D, et al. Epidural analgesia and intravenous patient-controlled analgesia result in similar rates of postoperative myocardial ischemia after aortic surgery. Anesth Analg 1997; 85: 1233–9.[Abstract]
13 Checketts MR, Gilhooly CJ, Kenny GN. Patient-maintained analgesia with target-controlled alfentanil infusion after cardiac surgery: a comparison with morphine PCA. Br J Anaesth 1998; 80: 748–51.
14 Turner RE. An evaluation of patient-controlled analgesia in adults undergoing cardiac surgery. S Afr Med J 1994; 84: 807–11.[Medline]
15 Gust R, Pecher S, Gust A, Hoffmann V, Bohrer H, Martin E. Effect of patient-controlled analgesia on pulmonary complications after coronary artery bypass grafting. Crit Care Med 1999; 27: 2218–23.[Medline]
16 Tsang J, Brush B. Patient-controlled analgesia in post-operative cardiac surgery. Anaesth Intensive Care 1999; 27: 464–70.[Medline]
17 Munro AJ, Long GT, Sleigh JW. Nurse-administered subcutaneous morphine is a satisfactory alternative to intravenous patient-controlled analgesia morphine after cardiac surgery. Anesth Analg 1998; 87: 11–5.
18 Boldt J, Thaler E, Lehmann A, Papsdorf M, Isgro F. Pain management in cardiac surgery patients: comparison between standard therapy and patient-controlled analgesia regimen. J Cardiothorac Vasc Anesth 1998; 12: 654–8.[Medline]
19 Myles PS, Buckland MR, Cannon GB, et al. Comparison of patient-controlled analgesia and nurse-controlled infusion analgesia after cardiac surgery. Anaesth Intensive Care 1994; 22: 672–8.[Medline]
20 O’Halloran P, Brown R. Patient-controlled analgesia compared with nurse-controlled infusion analgesia after heart surgery. Intensive Crit Care Nurs 1997; 13: 126–9.[Medline]
21 Gust R, Pecher S, Gust A, Hoffmann V, Bohrer H, Martin E. Effect of patient-controlled analgesia on pulmonary complications after coronary artery bypass grafting. Crit Care Med 1999; 27: 2218–23.[Medline]
22 Boulanger A, Perreault S, Choiniere M, Prieto I, Lavoie C, Laflamme C. Intrathecal morphine after cardiac surgery. Ann Pharmacother 2002; 36: 1337–43.[Abstract]
23 Pettersson PH, Lindskog EA, Owall A. Patient-controlled versus nurse-controlled pain treatment after coronary artery bypass surgery. Acta Anaesthesiol Scand 2000; 44: 43–7.[Medline]
24 Coyle JP, Steele J, Cutrone F, Higgins TL, Taylor PC. Patient controlled analgesia after cardiac surgery. Anesth Analg 1990; 70: S71.
25 Cepeda MS, Africano JM, Polo R, Alcala R, Carr DB. What decline in pain intensity is meaningful to patients with acute pain? Pain 2003; 105: 151–7.[Medline]
26 Farrar JT, Portenoy RK, Berlin JA, Kinman JL, Strom BL. Defining the clinically important difference in pain outcome measures. Pain 2000; 88: 287–94.[Medline]
27 Farrar JT, Berlin JA, Strom BL. Clinically important changes in acute pain outcome measures: a validation study. J Pain Symptom Manage 2003; 25: 406–11.[Medline]
28 Jensen MP, Chen C, Brugger AM. Interpretation of visual analog scale ratings and change scores: a reanalysis of two clinical trials of postoperative pain. J Pain 2003; 4: 407–14.[Medline]
29 Cheng DC, Karski J, Peniston C, et al. Morbidity out-come in early versus conventional tracheal extubation after coronary artery bypass grafting: a prospective randomized controlled trial. J Thorac Cardiovasc Surg 1996; 112: 755–64.
30 Ott E, Nussmeier NA, Duke PC, et al. Efficacy and safety of the cyclooxygenase 2 inhibitors parecoxib and valdecoxib in patients undergoing coronary artery bypass surgery. J Thorac Cardiovasc Surg 2003; 125: 1481–92.
31 Fitzpatrick GJ, Moriarty DC. Intrathecal morphine in the management of pain following cardiac surgery. A comparison with morphine i.v. Br J Anaesth 1988; 60: 639–44.
32 Chaney MA, Furry PA, Fluder EM, Slogoff S. Intrathecal morphine for coronary artery bypass grafting and early extubation. Anesth Analg 1997; 84: 241–8.[Abstract]
33 Chaney MA, Smith KR, Barclay JC, Slogoff S. Large-dose intrathecal morphine for coronary artery bypass grafting. Anesth Analg 1996; 83: 215–22.[Abstract]
34 Ho AM, Chung DC, Joynt GM. Neuraxial blockade and hematoma in cardiac surgery. Estimating the risk of a rare adverse event that has not (yet) occurred. Chest 2000; 117: 551–5.
35 Liu SS, Block BM, Wu CL. Effects of perioperative central neuraxial analgesia on outcome after coronary artery bypass surgery. A meta-analysis. Anesthesiology 2004; 101: 153–61.[Medline]
36 American Heart Association. Heart Disease and Stroke Statistics — 2005 Update. Dallas, Texas.: American Heart Association; 2005.
37 Rosseland LA, Stubhaug A. Gender is a confounding factor in pain trials: women report more pain than men after arthroscopic surgery. Pain 2004; 112: 248–53.[Medline]
This article has been cited by other articles:
 |
|
 |
|
  J. Katz, T. Buis, and L. Cohen Locked out and still knocking: predictors of excessive demands for postoperative intravenous patient-controlled analgesia: [Quand il n'y en a plus mais qu'on en veut encore : les predicteurs de besoins excessifs en analgesie postoperatoire intraveineuse controlee par le patient] Can J Anesth, February 1, 2008; 55(2): 88 - 99. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
