Controlled clinical trials in cancer pain. How controlled should they be? A qualitative systematic review.

This qualitative systematic review of the clinical methodology used in randomised, controlled trials of oral opioids (morphine, hydromorphone, oxycodone) for cancer pain underlines the difficulties of good pain research in palliative care. The current literature lacks placebo-controlled superiority trials. Recommendations for future research are discussed.

Perioperative ketamine for acute postoperative pain.

BACKGROUND: Postoperative pain management is often limited by adverse effects such as nausea and vomiting. Adjuvant treatment with an inexpensive opioid-sparing drug such as ketamine may be of value in giving better analgesia with fewer adverse effects. OBJECTIVES: To evaluate the effectiveness and tolerability of ketamine administered perioperatively in the treatment of acute postoperative pain in adults. SEARCH STRATEGY: Studies were identified from MEDLINE (1966-2004), EMBASE (1980-2004), the Cochrane Library (2004) and by handsearching reference lists from review articles and trials. The manufacturer of ketamine (Pfizer) provided search results from their in-house database, PARDLARS. SELECTION CRITERIA: Randomised controlled trials (RCTs) of adult patients undergoing surgery, being treated with perioperative ketamine or placebo. Studies where ketamine was administered in addition to a basic analgesic (such as morphine or NSAID) in one study group, and compared with a group receiving the same basic analgesic (but without ketamine) in another group, were also included. DATA COLLECTION AND ANALYSIS: Two independent reviewers identified fifty five RCTs for potential inclusion. Quality and validity assessment was performed by two independent reviewers. In the case of discrepancy, a third reviewer was consulted. Patient reported pain intensity and pain relief was assessed using visual analogue scales or verbal rating scales and adverse effects data were collated. MAIN RESULTS: Thirty-seven trials were included (2240 participants). Eighteen trials were excluded.Twenty-seven of the 37 trials found that perioperative subanaesthetic doses of ketamine reduced rescue analgesic requirements or pain intensity, or both. Quantitative analysis showed that treatment with ketamine reduced 24 hour PCA morphine consumption and postoperative nausea or vomiting (PONV). Adverse effects were mild or absent. AUTHORS' CONCLUSIONS: Ketamine in subanaesthetic dose (that is a dose which is below that required to produce anaesthesia) is effective in reducing morphine requirements in the first 24 hours after surgery. Ketamine also reduces postoperative nausea and vomiting. Adverse effects are mild or absent.

Peri-operative ketamine for acute post-operative pain: a quantitative and qualitative systematic review (Cochrane review).

BACKGROUND: Post-operative pain management is usually limited by adverse effects such as nausea and vomiting. Adjuvant treatment with an inexpensive opioid-sparing drug such as ketamine may be of value in giving better analgesia with fewer adverse effects. The objective of this systematic review was to evaluate the effectiveness and tolerability of ketamine administered peri-operatively in the treatment of acute post-operative pain in adults. METHODS: Studies were identified from MEDLINE (1966-2004), EMBASE (1980-2004), the Cochrane Library (2004) and by hand searching reference lists from review articles and trials. The manufacturer of ketamine (Pfizer AS, Lysaker, Norway) provided search results from their in-house database, PARDLARS. Randomized and controlled trials (RCTs) of adult patients undergoing surgery, being treated with peri-operative ketamine, placebo or an active control were considered for inclusion. RESULTS: Eighteen trials were excluded. Thirty-seven trials were included. Twenty-seven out of 37 trials found that peri-operative ketamine reduced rescue analgesic requirements or pain intensity, or both. Quantitative analysis showed that treatment with ketamine reduced 24-h patient-controlled analgesia (PCA) morphine consumption and post-operative nausea and vomiting (PONV). Adverse effects were mild or absent. CONCLUSION: In the first 24 h after surgery, ketamine reduces morphine requirements. Ketamine also reduces PONV. Adverse effects are mild or absent. These data should be interpreted with caution as the retrieved studies were heterogenous and the result of the meta-analysis can not be translated into any specific administration regimen with ketamine.

A bilateral clinical model for the study of acute and chronic pain after breast-reduction surgery.

BACKGROUND: There is a need for new clinical models to investigate effectively the development of pain after surgery and the effect, if any, of pre-emptive treatment. Bilateral models are of special interest, since the patient serves as his/her own control. The objective of this preliminary study was to test a clinical model for the study of acute and chronic pain after bilateral reduction mammoplasty. METHODS: Eight patients participated in the study where the breasts were randomized to test and control groups. In each patient, one breast was preoperatively infiltrated with lidocaine and adrenaline and the other breast infiltrated with saline and adrenaline. Assessment included visual analogue scale (VAS) pain intensity, thermal thresholds, mapping for punctate hyperalgesia and tactile sensation. Assessments were made preoperatively, postoperatively and at 6 months after surgery. RESULTS: With regard to acute postoperative pain intensity, the model demonstrated a clear difference between lidocaine and placebo treated breasts. There was no difference between lidocaine and placebo treated breasts with regard to chronic pain, but these results are inconclusive due to small number of patients. CONCLUSION: The model is sensitive and may be useful in studies of mechanisms of development and prevention of chronic pain after surgery.

[Childhood trauma and chronic pain]. / Barndomstraumer og kronisk smerte.

BACKGROUND: Chronic pain is a complex, multidimensional phenomenon. Medical intervention has often little effect. MATERIAL AND METHODS: The case histories of 100 patients evaluated by the multidisciplinary pain clinic team at Haukeland University Hospital in Bergen, Norway were examined. RESULTS: 44% of the patients reported serious trauma long before the development of pain. INTERPRETATION: Chronification of pain appears to be related to childhood trauma.

Low-dose subcutaneous ketamine infusion and morphine tolerance.

The NMDA receptor has been reported to be involved in opioid tolerance. Adjuvant subcutaneous infusion treatment with (very) low-dose ketamine, a NMDA receptor antagonist, improves analgesia and at the same time appears to reduce morphine tolerance. Three cases are presented.

[Practical problems associated with long-term opioid therapy]. / Praktiske problemer ved langvarig opioidbehandling.

Long-term opioid therapy results in physical dependency. Therefore abrupt cessation of opioid treatment may cause acute abstinence symptoms. The doses of opioids should always be reduced gradually, even when other treatment options give good pain relief. Patients receiving long-term treatment with opioids become more sensitive to the opioid antagonist naloxone. Inappropriate use of naloxone in these patients can also result in acute abstinence symptoms. Opioid treatment is limited by toxic side effects, and the problem can be solved by changing the opioid. The author describes three cases to illustrate these problems.

Typhoid fever in San Antonio, Texas: an outbreak traced to a continuing source.

Eighty cases of typhoid fever occurred in San Antonio, Texas, with dates of onset from August 18, 1981, to October 26, 1981. Preliminary epidemiological investigations of the first 24 cases suggested a Mexican food takeout restaurant as the common source. A case-control study confirmed this association (P less than or equal to .001). Barbacoa , a mixture of muscle, lips, ears, tongue, and eyes from steamed bovine heads, was identified as the source of Salmonella typhi (P = .03). S typhi was cultured from the stool of one of 31 restaurant employees. Closure of the restaurant resulted in termination of the outbreak within a single incubation period. The restaurant was allowed to reopen after the remaining employees had demonstrated lack of excretion of S typhi in stools. This outbreak represents the largest restaurant-associated typhoid fever outbreak reported in the United States in greater than 50 years.