Prospective Randomized Trial of Patient-Controlled Analgesia: DISCUSSION

6 Dec
2010

This prospective randomized study did not support the hypothesis that low-dose ketamine and morphine, administered in combination, would result in less pain than morphine alone. In addition, the combination therapy was not associated with less nausea and vomiting or fewer psychotomimetic effects than morphine alone, and there was no difference in the total amount of drug required.
In 2001, Burstal and others concluded that the potential usefulness of ketamine after hysterectomy was offset by a high incidence of adverse effects and that the combination of ketamine and morphine could not be recommended for routine care. These researchers used a 2:1 ratio of ketamine to morphine, whereas the current study used a 1:1 ratio; this difference may account for difference in frequency of adverse effects between the 2 studies (adverse effects were similar in the 2 groups in the current study). Sveticic and others analyzed 12 combinations of ketamine and morphine and found that a 1:1 ratio, with a lock-out period of 8 min, yielded optimum results. Sveticic and others17 reported lower pain scores and fewer side effects with the 1:1 ratio. We used a 1:1 ratio and a lock-out period of 6 min, almost identical with what is known as the “optimum combi­nation”, but were unable to reproduce the results of Sveticic and others. Viagra Super Active

The current study was underpowered because of the small sample size. The differences in outcomes did not reach statistical significance, but a trend was noted descriptively. Specifically, postoperative pain after abdominal hysterectomy was consistently higher with low-dose ketamine and morphine administered together by PCA device than with morphine alone (see Tables 2 and 3).
We used abdominal hysterectomy for this study because this surgical procedure was performed often at our hospital, which made patient enrollment easier, and because the use of PCA for managing postoperative pain is common for this type of surgery. In addition, patients undergoing total abdominal hysterectomy have a high risk of postoperative nausea and vomiting. In this study, there was no difference in pain between the 2 treatment groups; however, mean intensity of nausea and vomiting was higher for the morphine group on both postoperative days 1 and 2. Similarly, there was no difference in degree of dizziness, hallucinations, and dreams between the 2 groups on postoperative day 1 and very little difference on postoperative day 2. Interestingly, on postoperative day 1, fewer patients in the group receiving ketamine and morphine group experienced sedation.

The limitations of this study include the fact that it was not sufficiently powered to detect a small difference in outcomes. The small sample size means that the results obtained cannot be extended to the general population and must be interpreted with caution. In addition, it was not known whether the patients were opioid naive or if they were receiving psychotropic medications, as these data were not collected. Data were collected on postoperative days 1 and 2, but these intervals might have been too long; it might have been more meaningful to collect data every 4 or 6 h. In addition, postoperative nausea and vomiting might have been influenced by the effect not only of the morphine but also of general anesthesia, the timing of administra­tion of analgesia, the dose used, and the type of surgery. In this study, it was not possible to differentiate between these potentially explanatory factors. More importantly, nausea and vomiting were treated with antiemetics, including dimenhydrinate, metoclopramide, and ondansetron during the data-collection period, which could have affected the outcomes, even though validated data collection tools were used.
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CONCLUSIONS

In contrast to other studies, we found that the addition of ketamine to morphine for PCA did not reduce pain scores or adverse effects for patients who had undergone abdominal hysterectomy.

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