Objective:To quantify the physical and chemical stability data published for commonly used continuously infused medications in the intensive care unit and to evaluate the quality of the studies providing these data.Data Sources and Study Selection:We conducted a systematic electronic literature sear

Systematic review of physical and chemical compatibility of commonly used medications administered by continuous infusion in intensive care units.

Efforts to develop new hypnotic compounds continue, although several have recently failed in development. Propofol has been reformulated in various presentations with and without preservatives. Pharmacokinetic and pharmacodynamic differences exist between some of these preparations, and it is currently unclear whether any have substantial advantages over the original presentation. The use of target-controlled infusion (TCI) has been extended to include paediatric anaesthesia and sedation. Application of TCI to remifentanil is now licensed. Linking of electroencephalogram (EEG) monitoring to TCI for closed-loop anaesthesia remains a research tool, although commercial development may follow. The availability of stereoisomer ketamine and improved understanding of its pharmacology have increased non-anaesthetic use of ketamine as an adjunct analgesic. It may be useful in subhypnotic doses for postsurgical patients with pain refractory to morphine administration.

Recent advances in intravenous anaesthesia

assigned to receive, during the postoperative period, either i.v. morphine 1 mg ml 21 or morphine with ketamine 1 mg ml 21 for each. Morphine consumption was evaluated by cumulative doses every 12 h for the three postoperative days. Postoperative respiratory disorders were assessed by spirometric evaluation and recording of nocturnal desaturation. Results. The adjunction of ketamine resulted in a significant reduction in cumulative morphine consumption as early as the 36th postoperative hour [43 (SD 18) vs 32 (14) mg, P¼0.03] with a similar visual analogue scale. In the morphine group, the percentage of time with desaturation ,90% was higher during the three nights [1.80 (0.21‐6.37) vs 0.02 (0‐0.13), P,0.001; 2.15 (0.35‐8.65) vs 0.50 (0.01‐1.30), P¼0.02; 2.46 (0.57‐5.51) vs 0.55 (0.21‐1.00), P¼0.02]. The decrease in forced expiratory volume in 1 s was less marked in the ketamine group at the first postoperative day [1.04 (0.68‐1.22) litre vs 1.21 (1.10‐0.70) litre, P¼0.039]. Conclusions. Adding small doses of ketamine to morphine in PCA devices decreases the morphine consumption and may improve respiratory disorders after thoracic surgery.

Adding ketamine to morphine for patient-controlled analgesia after thoracic surgery: influence on morphine consumption, respiratory function, and nocturnal desaturation

Recent data in animal experiments as in clinical trials have clearly reported that pain modulation is related to an equilibrium between antinociceptive and pronociceptive systems. Therefore, the apparent pain level could not only be a consequence of a nociceptive input increase but could also result from a pain sensitization process. Glutamate, via NMDA receptors, plays a major role in the development of such a neuronal plasticity in the central nervous system, leading to a pain hypersensitivity that could facilitate chronic pain development. By an action on NMDA receptors opioids also induce, in a dose dependent manner, an enhancement of this postoperative hypersensitivity. "Antihyperalgesic" doses of ketamine, an NMDA receptor antagonist, were able to decrease this central sensitization not only in painful animal but also in human volunteers exposed to different pain models, or in the postoperative period. Many studies have reported that ketamine effects are elicited when this drug is administered the following manner: peroperative bolus (0.1 to 0.5 mg/kg), followed by a constant infusion rate (1 to 2 microg/kg per min) during the peroperative period and for 48 to 72 hours after anaesthesia. Those ketamine doses improved postoperative pain management by reducing hyperalgesia due to both surgical trauma and high peroperative opioid doses. This antihyperalgesic action of ketamine also limited the postoperative morphine tolerance leading to a decrease in analgesic consumption and an increase in the analgesia quality.

Kétamine à faibles doses : antihyperalgésique, non analgésique

Background: Pain following embolization of the uterine arteries (UAEs) is variable and may be very severe requiring large doses of parenteral opioids for relief. The present study tested the hypothesis that the addition of ketamine to IV patient-controlled morphine reduces the amount of morphine required for pain-control during the first 24 h after UAE embolization.



Methods: Fifty-six patients undergoing UAE embolization for treatment of symptomatic uterine leiomyomata were randomized to receive either 2 mg/ml of morphine (Control group, n=30) or 2 mg/ml of both morphine and ketamine (Ketamine group, n=26) by IV patient-controlled analgesia (IV-PCA). Pump settings were bolus dose 1 ml, lockout 10 min, no background infusion. In addition, all patients received diclofenac and acetaminophen for pain relief. Pain scores, morphine consumption and adverse events like nausea, vomiting, itching, visual disturbances, anxiety, dreaming and hallucinations, if any, were recorded for 24 h after embolization.



Results: The mean ± SD 24-h consumption of patient-controlled morphine was 38.3 ± 21.0 mg in the Ketamine group vs. 33.3 ± 18.3 mg in the Control group (NS). The difference between the means was 5.0 mg (95% confidence interval: −5.7; 15.6). One patient in the Ketamine group vs. none in the Control group experienced auditory hallucinations.



Conclusion: Studying an unselected group of patients undergoing embolization of the UAEs for treatment of symptomatic uterine leiomyomata under conditions of basal analgesia with acetaminophen and diclofenac, we failed to demonstrate any morphine-sparing effect of IV-PCA ketamine and morphine compared with IV-PCA morphine alone.

No morphine sparing effect of ketamine added to morphine for patient‐controlled intravenous analgesia after uterine artery embolization

UNLABELLED Recent advances in acute pain mechanisms and management have implicated the N-methyl D-aspartate receptor-ion channel complex in the development of postoperative hyperalgesia and acute opioid tolerance. N-methyl D-aspartate receptor antagonists such as ketamine have been used increasingly in clinical studies in an effort to minimize acute postoperative pain and reduce opioid requirements. A mixture of ketamine and an opioid administered in the same solution and syringe would be a practical and useful technique for postoperative epidural analgesia, continuous IV infusion, or patient-controlled IV analgesia. We investigated the stability of a morphine sulfate and racemic ketamine solution in saline at pH 5.5-7.5 over a period of 4 days. Our study demonstrates that the ketamine-morphine mixture at a clinically relevant concentration seems to be stable at room temperature, at a wide range of pH values, for at least 4 days. IMPLICATIONS Small-dose ketamine is used with increasing frequency in the acute postoperative setting as an adjunct to traditional opioid analgesics. We show that a racemic ketamine and morphine solution at a clinically relevant concentration seems to be stable at room temperature at a wide range of pH values for at least 4 days.

/pdf/the-stability-of-a-ketamine-morphine-solution-13zgibleyl.pdf

The stability of a ketamine-morphine solution.

https://link.springer.com/content/pdf/10.1007/BF03016966.pdf

Roger Schmid

Papers

The stability of a ketamine-morphine solution.

Postop pain & morphine are reduced by perioperative multimodal analgesia