Objective: The aim was to compare the effects of low tidal volume (VT) and moderate positive end-expiratory pressure (PEEP) with high VT and zero end-expiratory pressure (ZEEP) on postoperative pulmonary functions and oxygenation in patients undergoing robot-assisted laparoscopic radical prostatectomy. Subjects and Methods: Forty-four patients were randomized into low VT-PEEP and high VT-ZEEP groups. The patients were ventilated with a VT of 6 mL/kg and 8 cm H2O PEEP in the low VT-PEEP group and a VT of 10 mL/kg and 0 cm H2O PEEP in the high VT-ZEEP group. Preoperative and postoperative spirometric measurements were done and chest X-rays were evaluated using the radiological atelectasis score (RAS). p < 0.05 was considered statistically significant. Results: The intraoperative and postoperative arterial partial pressure of oxygen and arterial oxygen saturation values were significantly higher in the low VT-PEEP group than in the high VT-ZEEP group. At all times, the arterial-to-alveolar oxygenation gradients were significantly lower in the low VT-PEEP group than in the high VT-ZEEP group. Preoperative RAS were similar in both groups, but the postoperative RAS was significantly lower in the low VT-PEEP group (p < 0.001). Forced vital capacity, forced expiratory volume in 1 s, and peak expiratory flow rate recorded postoperatively were significantly lower in the high VT-ZEEP group (p < 0.001). Conclusions: Postoperative pulmonary functions were less impaired in patients ventilated with a VT of 6 mL/kg and 8 cm H2O PEEP than in patients ventilated with a VT of 10 mL/kg and ZEEP.
Active subdiaphragmatic gas aspiration after a laparoscopic cholecystectomy is a simple procedure that can effectively reduce postoperative abdominal and shoulder pain and as a result the need for analgesics.
Perioperative uses of low dose ketamine decreased post-operative opioid requirements, which was observed long after the normal expected duration of ketamine.
Carbonic anhydrase-8 (Car8 mouse gene symbol) is devoid of enzymatic activity, but instead functions as an allosteric inhibitor of inositol trisphosphate receptor-1 (ITPR1) to regulate this intracellular calcium release channel important in synaptic functions and neuronal excitability. Causative mutations in ITPR1 and carbonic anhydrase-8 in mice and humans are associated with certain subtypes of spinal cerebellar ataxia (SCA). SCA mice are genetically deficient in dorsal root ganglia (DRG) Car8 expression and display mechanical and thermal hypersensitivity and susceptibility to subacute and chronic inflammatory pain behaviors in mice. In this report we show that DRG Car8 expression is variable across 25 naive-inbred strains of mice, and this cis-regulated eQTL (association between rs27660559, rs27706398, and rs27688767 and DRG Car8 expression; P<1×10−11) is correlated with nociceptive responses in mice. Next, we hypothesized that increasing DRG Car8 gene expression would inhibit intracellular calcium release required for morphine antinociception and might correlate with antinociceptive sensitivity of morphine and perhaps other analgesic agents. We show that mean DRG Car8 gene expression is directly related to the dose of morphine or clonidine needed to provide a half-maximal analgesic response (r=0.93, P<0.00002; r=0.83, P<0.0008, respectively), suggesting that greater DRG Car8 expression increases analgesic requirements. Finally, we show that morphine induces intracellular free calcium release using Fura 2 calcium imaging in a dose-dependent manner; and V5-Car8WT overexpression in NBL cells inhibits morphine-induced calcium increase. These findings highlight the ‘morphine paradox’ whereby morphine provides antinociception by increasing intracellular free calcium, while Car8 and other antinociceptive agents work by decreasing intracellular free calcium. This is the first study demonstrating that biologic variability associated with this cis-eQTL may contribute to differing analgesic responses through altered regulation of ITPRI-dependent calcium release in mice.
Recently, we showed murine DRG Car8 expression is a cis-regulated eQTL that determines analgesic responses. In this report, we show transduction via SN injection of DRG with human wildtype CA8 using AAV viral particles (AAV8-V5-CA8WT) produces analgesia in naïve male C57BL/6J mice and anti-hyperalgesia after carrageenan treatment. A peak mean increase of about 4 seconds in thermal hindpaw withdrawal latency equaled increases in thermal withdrawal latency produced by 10 mg/kg IP morphine in these mice. Allometric conversion of this IP morphine dose in mice equals an oral morphine dose of about 146 mg in a 60 kg adult. Our work quantifies for the first time analgesia and anti-hyperalgesia in an inflammatory pain model after DRG transduction by CA8 gene therapy.
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