The relationship between movement-evoked versus spontaneous pain and peak expiratory flow after abdominal hysterectomy

The pathogenesis of postoperative lung dysfunction implies a role for movement-evoked pain (e.g., splinting/hypoventilation because of pain avoidance). However, interactions between evoked pain and respiratory physiology are poorly understood. Thus, we examined the relationship between evoked versus spontaneous pain and one index of pulmonary function. In 25 patients having undergone a hysterectomy, visual analog scale ratings (100 mm) for spontaneous pain (REST) and pain during sitting (SIT), forced expiration (BLOW), and coughing (COUGH) were measured together with peak expiratory flow (PEF) at eight time points during postoperative Days 1 and 2. Secondary outcome measures included oxygen saturation and oxygen requirements. Pain was significantly correlated with PEF for COUGH, SIT, BLOW, and REST at eight, seven, four, and two of the eight studied time points, respectively. Mean visual analog scale scores [SE] for COUGH (26.1 mm [1.7]) and SIT (21.5 mm [1.5]) were greater (P < 0.05) than REST (10.5 mm [0.8]), and COUGH was greater (P < 0.05) than BLOW (16.8 mm [1.3]). All pain measures diminished (P < 0.05), and PEF reductions improved (P < 0.05) across the study period. We hypothesize that the consistent negative correlation of COUGH-evoked pain with PEF is, in part, caused by avoidance of coughing, which ultimately limits deep inspiration, lung reexpansion, and clearance of secretions. IMPLICATIONS: Movement-evoked pain may be an important contributor to postoperative complications, but its mechanisms are poorly understood. This study provides the first evidence that postoperative evoked pain correlates with lung function and highlights the need for future research on mechanisms and implications of this phenomenon.     

Single-dose haloperidol for the prophylaxis of postoperative nausea and vomiting after intrathecal morphine

Postoperative nausea and vomiting (PONV) occurs frequently with the use of intrathecal morphine. We studied the ability of a single, small dose of the inexpensive, long-acting, dopamine receptor-blocking drug, haloperidol, to prevent PONV after spinal anesthesia using local anesthetic with morphine 0.3 mg. One-hundred-eight adult patients undergoing elective lower limb orthopedic or endoscopic urologic procedures under spinal anesthesia were randomized to receive IM haloperidol 1 mg (H1), haloperidol 2 mg (H2), or placebo (P) after an intrathecal injection. Patients were assessed for 24 h after surgery, with treatment failure being defined as nausea >1 on a 10-cm visual analog scale or any vomiting or request for rescue antiemetic. Most treatment failures occurred during the first 12 h (60% overall), and haloperidol led to a dose-dependent decrease in PONV (first 12 h: 76% P, 56% H1, and 50% H2; P = 0.012). A history of PONV was strongly associated with PONV in the current study, regardless of treatment group. There were no dystonic reactions noted to either dose of haloperidol. We conclude that haloperidol reduces the incidence of PONV after intrathecal morphine, although this incidence remains a significant problem even with treatment. IMPLICATIONS: In this randomized, double-blinded, placebo-controlled trial, a single, small IM dose of haloperidol 1 mg or 2 mg reduced the incidence of postoperative nausea and vomiting after spinal anesthesia with local anesthetic and intrathecal morphine.     

Ovarian insufficiency and early pregnancy loss induced by activation of the innate immune system

We describe a murine model of early pregnancy failure induced by systemic activation of the CD40 immune costimulatory pathway. Although fetal loss involved an NK cell intermediate, it was not due to lymphocyte-mediated destruction of the fetus and placenta. Rather, pregnancy failure resulted from impaired progesterone synthesis by the corpus luteum of the ovary, an endocrine defect in turn associated with ovarian resistance to the gonadotropic effects of prolactin. Pregnancy failure also required the proinflammatory cytokine TNF-alpha and correlated with the luteal induction of the prolactin receptor signaling inhibitors suppressor of cytokine signaling 1 (Socs1) and Socs3. Such links between immune activation and reproductive endocrine dysfunction may be relevant to pregnancy loss and other clinical disorders of reproduction.