IntroductionRecent advances in operative procedures and surgical instrumentation have enabled the application of laparoscopic techniques to more complex surgeries. However, complex procedures require extended insuffl ation times (typically greater than 3 hours) 1-6 and consequently patients undergo prolonged periods of elevated intraabdominal pressure. And while the benefi ts of using minimally invasive techniques for longer procedures are presumed to be similar to those obtained for "simple" laparoscopic surgeries, it is now recognized that carbon dioxide (CO 2 ) pneumoperitoneum and the resultant rise in intra-abdominal pressure can produce reductions in organ blood fl ow, acidosis, and alterations in cardiovascular and respiratory status, 5-10 all of which can impact postoperative organ function and patient recovery; the severity of these eff ects correlates to the duration of insuffl ation. 11To some extent, the acidosis and systemic effects of pneumoperitoneum can be controlled by altering ventilation rates and/or administration of vasoactive agents but such interventions have minimal ability to preserve end-organ blood fl ow and oxygen delivery. Th is is because local tissue blood fl ow, rather than blood oxygen content, is the primary determinant of oxygen delivery. Local tissue perfusion is regulated by a physiological response termed hypoxic vasodilation in which tissue oxygen requirements are directly coupled to blood fl ow, the domain of nitric oxide (NO) bioactivity.12 Second to second changes in microcirculatory fl ow are controlled by complex interactions between oxygen, NO, and hemoglobin (Hb) within the red blood cell with Hb serving as an oxygen sensor and as a hypoxia-responsive transducer of NO signals. 13,14 Vasodilation by S-nitrosoHb (SNO-Hb; i.e., release of NO bioactivity) is linked to Hb desaturation and provides a regulated mechanism for matching blood fl ow and oxygen delivery with local metabolic demand. 15Decreased levels and/or impaired processing of SNO-Hb have been observed in disparate diseases characterized by tissue hypoxemia; [16][17][18][19][20][21][22] where examined, red blood cells from these patients exhibited impaired vasodilatory capacity. Such data suggest that red blood cell derived NO bioactivity plays an important role in the respiratory cycle and that impairment of this activity might contribute to the pathophysiology of ischemic conditions. Based on these fi ndings, we reasoned that insuffl ationinduced reductions in splanchnic blood fl ow may be due, at least in part, to alterations (reductions) in SNO-Hb homeostasis. By extension, an intervention directed toward increasing NO bioactivity could potentially ameliorate pneumoperitoneuminduced reductions in organ blood fl ow. Th eoretical support for this hypothesis comes from the observations that reductions in blood pH, as occur during CO 2 pneumoperitoneum, accelerate SNO-Hb decay 23,24 and increased mechanical ventilation (as may be initiated to control hybercarbia) increases the concentration of exhaled NO 25 b...

Any adverse preterm fetal response to maternal surgery should not be attributed solely to the actions of general anesthesia upon the fetus.

Topics: Pharmacology P regnant women may require sedation, anesthesia, or pain control for nonobstetric-related care. The a 2adrenergic receptor (a 2 AR) agonist dexmedetomidine (DEX) has sedative, anxiolytic, and analgesic actions and can reduce the dose requirements for other sedative and analgesic drugs through synergistic effects with opioids and benzodiazepines. Clinical investigations of DEX have not included significant numbers of pregnant patients; in fact, most studies have excluded pregnant women. This study was designed to determine the maternal and fetal responses to an intravenous infusion of DEX in sheep.The study was performed on 9 preterm pregnant ewes at gestational day 92, a time relatively equivalent to the end of the second trimester in humans. Surgical anesthesia was induced with IV sodium thiopental and maintained with isoflurane in oxygen. Standard surgical techniques were used to insert catheters into maternal femoral artery and jugular vein as well as bilateral fetal femoral arteries. A flow probe was placed around the left uterine artery to record uterine blood flow (UBF). The fetal head was exteriorized to install near-infrared spectroscopy probes to assess changes in fetal cerebral oxygenation during and after drug administration to the mother. The fetus was then returned to the uterus. After the procedure, infiltration of the surgical incision with bupivacaine and intramuscular nalbuphine hydrochloride were used to control postoperative pain. Animals recovered for 48 hours before the DEX-exposure experiment was conducted. Maternal and fetal cardiovascular data along with UBF were recorded. Fetal cerebral oxygenation, measured by changes in oxygenated, deoxygenated, and total hemoglobin (Hb) (oxyHb, deoxyHb, and totalHb, respectively), was quantitated with the near-infrared spectroscopy monitor. After a baseline recording period of 30 to 60 minutes, drug exposure was begun using human-dosing guidelines. Each ewe received an IV bolus injection of DEX, 1.0 mg/kg followed by a constant IV infusion of 1.0 mg/kg/h. The infusion was stopped after 3 hours and the experiment halted 2 hours later. Hemodynamic and fetal cerebral oxygenation data were continuously recorded during the study; maternal and fetal arterial blood samples were obtained at 30-minute intervals.The statistical analyses focused on the 3 primary endpoints: changes in fetal cerebral oxygenation, maternal and fetal cardiovascular status, and arterial blood gas status.All animals tolerated the DEX infusion with no complications during or after drug exposure. Profound sedation occurred within minutes of starting the infusion; consciousness returned within 30 to 60 minutes after discontinuation of the infusion. During the infusion, the sheep were unresponsive to painful stimuli. The ewes had a normal respiratory pattern throughout the exposure period, as evidenced by the arterial blood gas values that remained normal throughout the study. Only blood glucose levels in both the ewe and fetus continued to rise during DEX infusion, p...

Background The α2 adrenergic receptor agonist dexmedetomidine has some unique pharmacologic properties that could benefit pregnant patients (and their fetuses) when they require sedation, analgesia, and/or anesthesia during pregnancy. The purpose of the present study was to delineate maternal and fetal responses to an intravenous infusion of dexmedetomidine. Methods This study was conducted on surgically-recovered preterm sheep instrumented for physiologic recording and blood sampling. Maternal and fetal cardiovascular and blood gas parameters and fetal cerebral oxygenation levels were recorded before, during, and after 3 h of dexmedetomidine infusion to the ewe at a rate of 1 μg/kg/h. Results Drug infusion produced overt sedation but no apparent respiratory depression as evidenced by stable maternal arterial blood gases; fetal blood gases were also stable. The one blood parameter to change was serum glucose, By the end of the 3 h infusion, glucose increased from 49 ± 10 to 104 ± 33 mg/dL in the ewe and from 22 ± 3 to 48 ± 16 mg/dL in the fetus; it declined post-drug exposure but remained elevated compared to the starting levels (maternal, 63 ± 12 mg/dL, P = 0.0497; and fetal, 24 ± 4 mg/dL, P = 0.012). With respect to cardiovascular status, dexmedetomidine produced a fall in maternal blood pressure and heart rate with fluctuations in uterine blood flow but had no discernable effect on fetal heart rate or mean arterial pressure. Likewise, maternal drug infusion had no effect on fetal cerebral oxygenation, as measured by in utero near-infrared spectroscopy. Conclusions Using a clinically-relevant dosing regimen, intravenous infusion of dexmedetomidine produced significant maternal sedation without altering fetal physiologic status. Results from this initial acute assessment support the conduct of further studies to determine if dexmedetomidine has clinical utility for sedation and pain control during pregnancy.

Objectives: This study has investigated the efficacy and safety of daikenchuto (DKT) in elderly patients with fecal incontinence (FI). Methods:This was an open-label, single-arm study (UMIN Clinical Trials Registry as UMIN000030252). DKT at 15 g/day was orally administered to patients for 28 days. Patients over 70 years old with FI, who scored over 11 in the Mini-Mental State Examination, are capable of oral intake, and provided written informed consent, were enrolled in this study. Changes in abdominal pain and bloating, Cleveland Clinic Incontinence Score (CCIS), FI Quality of Life Scale (FIQLS), maximum resting pressure (MRP), FI frequency, and stool form were evaluated. Results: In total, 21 patients (1 requested to withdraw) were enrolled in this study. The compliance rate was 95.2%, and no serious adverse drug reactions were observed. Improvements in terms of abdominal pain and bloating were observed at 2 weeks (p < 0.01). In the CCIS, the total score, leakage of solid stool, and leakage of liquid stool improved after 2 weeks (p < 0.01), while pad use and lifestyle alteration improved after 4 weeks (p < 0.05). Improvement in FIQLS was also observed at 2 weeks (p < 0.01). MRP demonstrated significant improvement at 2 weeks (p < 0.01). Eleven (52.4%) patients had no FI during the study period. Conclusions: DKT improves MRP and quality of life in patients with abdominal symptoms; moreover, it is considered to be a safe and effective drug for elderly patients with FI.