A randomized, single-blind, increasing dose safety trial of an oxygen-carrying plasma expander (Hemospan) administered to orthopaedic surgery patients with spinal anaesthesia.

The objective of this study was to further explore the safety of Hemospan (Sangart Inc., San Diego, CA, USA), an oxygen-carrying plasma expander. The aim of this study was to determine if Hemospan is well tolerated in orthopaedic surgery patients with spinal anaesthesia in doses up to 1 L. Hemospan was previously found to be well tolerated in normal volunteers and orthopaedic surgery patients with spinal anaesthesia in doses up to 500 mL. Five cohorts of six orthopaedic surgery patients, American Society of Anesthesiologists (ASA) I and II, were studied. In each cohort, four patients received Hemospan in doses ranging from 200 to 1000 mL, and two received Ringer's lactate immediately prior to induction of spinal anaesthesia. There were no serious adverse events (SAEs). Iohexol clearance measured before and 24 h after dosing was unaffected. There were 14 adverse events (AEs) in the 10 control patients (1.4 per patient) and 30 in the 20 patients receiving Hemospan (1.5 per patient). One patient in the group receiving 200 mL Hemospan had elevated mean arterial pressure after dosing, but there were no elevations in any of the other patients. The peak plasma Hemospan concentration in the 1000 mL group was 1.3 g dL(-1), with a dose-dependent clearance (T(1/2)) ranging from 14.1 to 23.0 h. Plasma methaemoglobin levels were independent of dose, reaching a maximum at 40 h after dosing and never exceeded 0.125 g dL(-1). Troponin T was transiently elevated in two patients receiving Hemospan without symptoms or electrocardiographic abnormalities or elevation of myocardial creatinine kinase isoenzyme. Hemospan was well tolerated in this group of patients at doses up to 1000 mL.

Low-dose bupivacaine with sufentanil prevents hypotension after spinal anesthesia for hip repair in elderly patients.

BACKGROUND: Hip fracture is common in the geriatric population. Patients in this group are often at high risk for perioperative complications from concurrent diseases. Conventional spinal anesthesia can be associated with hypotension but has a better postoperative outcome compared to general anesthesia. We judged that a reduced dose of bupivacaine in combination with sufentanil could give reliable blocks with minimal hypotension. METHODS: Fifty elderly patients were randomized into two groups. The study group received spinal anesthesia as a combination of hyperbaric bupivacaine 7.5 mg and sufentanil 5 microg while the control group received hyperbaric bupivacaine 15 mg. The hemodynamic stability of the patients and the quality of the blocks were compared. RESULTS: All patients had adequate duration of reliable blocks. More control group patients than study group patients required ephedrine due to hypotension. CONCLUSION: A reduced dose of hyperbaric bupivacaine (7.5 mg) in combination with sufentanil (5 microg) provides reliable spinal anesthesia for the repair of hip fracture in aged patients with few events of hypotension and little need for vasopressor support of blood pressure.

Diclofenac in the treatment of pain after caesarean delivery. An opioid-saving strategy.

OBJECTIVE: Pain relief of good quality after caesarean section (CS) results in early mobilization and good early mother-child interaction. Patient-controlled analgesia (PCA), with systemic opioids, gives a very high level of patient satisfaction. However, opioids have well documented side-effects i.e. sedation, nausea and respiratory depression. To minimize the risk of such negative effects we studied how far the required dose of opioid could be decreased with a multimodal strategy adding diclofenac. STUDY DESIGN: In a randomized double-blind study, 50 parturients scheduled for elective CS under spinal anaesthesia, received rectally either diclofenac (Suppositorium diclofenac) 50 mgx3 or placebo 1x3 during the first 24 h postoperatively. All patients had PCA with the possibility of self-administered doses of ketobemidone 1 mg/6 min. RESULTS: In the group receiving diclofenac rectally the consumption of ketobemidone was reduced with 39% compared to the placebo group. CONCLUSION: A multimodal analgetic strategy with the addition of 150 mg diclofenac during the first 24 h after CS reduces the need for opioids significantly with maintained or improved analgetic effect. This is expected to reduce the risk of negative side-effects of systemic opioids.

Effects of dextromethorphan in clinical doses on capsaicin-induced ongoing pain and mechanical hypersensitivity.

The analgesic properties of the noncompetitive N-methyl-D-aspartate (NMDA)-receptor antagonist dextromethorphan, available for clinical use as an antitussive, have been studied in the human capsaicin pain model to determine a possible clinical effect on pain due to central sensitization. Ninety milligrams dextromethorphan or vehicle was given orally to ten volunteers, each at two different occasions in a double-blind fashion, prior to an intradermal injection of 300 micrograms capsaicin. Ongoing pain, pain evoked by von Frey filament stimulation, and pressure pain thresholds were assessed before and after the capsaicin injection. The area in which von Frey filament stimulation evoked pain was mapped after the capsaicin injection. There were no significant group effects on ongoing pain, or on von Frey or pressure hypersensitivity. There was also no significant effect on the area of mechanical hypersensitivity. These results show that clinical doses of dextromethorphan do not effect ongoing or mechanically evoked pain after capsaicin injection.

Peripherally administrated morphine attenuates capsaicin-induced mechanical hypersensitivity in humans.

We examined the hypothesis that peripheral morphine can modulate pain and hyperalgesia/allodynia in the human capsaicin model. Subcutaneous injections of 1 mL morphine (1 mg/mL) in one arm and of 1 mL 0.9% saline in the other arm were made prior to bilateral intradermal injections of 50 microL (6 mg/mL) capsaicin. All injections were made on the volar aspect of the arm. Before and after the capsaicin injections, spontaneous pain and pain evoked by repetitive von Frey filament stimulation was rated on a numerical rating scale; furthermore, pressure pain thresholds were determined. The area in which von Frey filament stimulation evoked pain and the area of visible flare were mapped after the capsaicin injection. Capsaicin injection resulted in spontaneous pain on the saline-injected side not significantly different from that on the morphine-injected side. However, capsaicin injections gave rise to significantly less pain evoked by mechanical stimuli, as well as to a significantly smaller area of mechanical hypersensitivity, on the morphine-injected side compared with the saline-injected side. These results suggest that morphine can modulate sensitization mechanisms involved in the development of capsaicin-induced mechanical hypersensitivity.

Peripheral alpha-adrenoreceptors are involved in the development of capsaicin induced ongoing and stimulus evoked pain in humans.

While the sympathetic nervous system seems to be involved in some pain states, the mechanisms linking the sensory and sympathetic nervous system are unclear. In this study the possible involvement of peripheral alpha-adrenoreceptors in the development of capsaicin induced ongoing pain and mechanical hypersensitivity was examined in humans. Intradermal capsaicin injections in the volar aspect of the arm gave rise to ongoing burning pain and dysesthesia as well as mechanical hypersensitivity. Ongoing pain and pain evoked by von Frey filament stimulation was rated on a numerical rating scale after intradermal capsaicin injection. The area of skin in which von Frey filament stimulation evoked pain was measured. A subcutaneous injection of phentolamine (alpha-adrenoreceptor antagonist) on one side and saline on the other side prior to the capsaicin injection was done to evaluate the role of the peripheral alpha-adrenoreceptors in development of capsaicin induced sensory symptoms and signs. Significantly less ongoing and evoked pain developed on the phentolamine injected side compared to the saline side, the latter in the area adjacent to the capsaicin injection (primary zone) and well outside the area of flare (secondary zone). The area in which pain could be evoked on the phentolamine injected side was restricted to the area of flare and was significantly smaller than on the saline injected side. Mechanical stimulation gave rise to aftersensation and radiation of pain on the saline injected side in all subjects but only in one case on the phentolamine injected side. Peripheral alpha-adrenoreceptors thus seem to be involved in functional changes of primary afferents which contribute to ongoing pain and mechanical stimulus evoked pain.

Long-term therapy with subcutaneous heparin during pregnancy.

35 pregnant women (37 pregnancies) were treated with subcutaneous and/or intravenous heparin because of acute thromboembolic complications (TE) or as prophylaxis against TE. 25 pregnancies were uncomplicated. The most frequent complication was incipient premature labor, which occurred in 7 women. Other complications were retention placentae, twin pregnancies, ablatio placentae and minor hematomas. No serious bleeding complications occurred. The treatment did not seem to affect the children. The antithrombin III (AT) level measured with the chromogenic substrate, S-2238, and platelet counts were analyzed in 16 women. Liver function was studied in 13 of them. A significant decrease in AT occurred initially in both groups and normalization was noted during long-term heparin treatment. Platelet count and liver function were mainly unchanged.