Recruitable alveolar collapse and overdistension during laparoscopic gynecological surgery and mechanical ventilation: a prospective clinical study

Background Laparoscopic surgery in Trendelenburg position may impede mechanical ventilation (MV) due to positioning and high intra-abdominal pressure. We sought to identify the positive end-expiratory pressure (PEEP) levels necessary to counteract atelectasis formation ("Open-Lung-PEEP") and to provide an equal balance between overdistension and alveolar collapse ("Best-Compromise-PEEP"). Methods Results In supine position, the median Open-Lung-PEEP was 12 (8-14) cmH2O with 8.7 (4.7-15.5)% of overdistension and 1.7 (0.4-2.2)% of collapse. Best-Compromise-PEEP was 8 (6.5-10) cmH2O with 4.2 (2.4-7.2)% of overdistension and 5.1 (3.9-6.5)% of collapse. In Trendelenburg position with capnoperitoneum, Open-Lung-PEEP was 18 (18-20) cmH 2 O (p < 0.0001 vs supine position) with 1.8 (0.5-3.9)% of overdistension and 0 (0-1.2)% of collapse and Best-Compromise-PEEP was 18 (16-20) cmH2O (p < 0.0001 vs supine position) with 1.5 (0.7-3.0)% of overdistension and 0.2 (0-2.7)% of collapse. Open-Lung-PEEP and Best-Compromise-PEEP were positively correlated with body mass index during MV in supine position but not in Trendelenburg position. Conclusion The PEEP levels required for preventing alveolar collapse and for balancing collapse and overdistension in Trendelenburg position with capnoperitoneum were significantly higher than those required for achieving the same goals in supine position without capnoperitoneum. Even with high PEEP levels, alveolar overdistension was negligible during MV in Trendelenburg position with capnoperitoneum. Trial registration This study was prospectively registered at German Clinical Trials registry (DRKS00016974)

Influence of clonidine and ketamine on m-RNA expression in a model of opioid-induced hyperalgesia in mice.

We investigated the influence of morphine and ketamine or clonidine in mice on the expression of genes that may mediate pronociceptive opioid effects.C57BL/6 mice received morphine injections thrice daily using increasing doses (5-20 mg∙kg(-1)) for 3 days (sub-acute, n=6) or 14 days (chronic, n=6) and additionally either s-ketamine (5 mg∙kg(-1), n=6) or clonidine (0.1 mg∙kg(-1), n=6). Tail flick test and the assessment of the mechanical withdrawal threshold of the hindpaw was performed during and 4 days after cessation of opioid treatment. Upon completion of the behavioural testing the mRNA-concentration of the NMDA receptor (NMDAR1) and β-arrestin 2 (Arrb2) were measured by PCR.Chronic opioid treatment resulted in a delay of the tail flick latency with a rapid on- and offset. Simultaneously the mice developed a static mechanical hyperalgesia with a delayed onset that that outlasted the morphine treatment. Sub-acute morphine administration resulted in a decrease of NMDAR1 and Arrb2 whereas during longer opioid treatment the expression NMDAR1 and Arrb2 mRNA increased again to baseline values. Coadministration of s-ketamine or clonidine resulted in a reversal of the mechanical hyperalgesia and inhibited the normalization of NMDAR1 mRNA expression but had no effect on the expression of Arrb2 mRNA.In the model of chronic morphine therapy the antinociceptive effects of morphine are represented by the thermal analgesia while the proniceptive effects are represented by the mechanical hyperalgesia. The results indicate that the regulation of the expression of NMDAR1 and Arrb2 may be associated to the development of OIH in mice.The results indicate that co-administration of clonidine or ketamine may influence the underlying mechanisms of OIH

Adjustment of positive end-expiratory pressure to body mass index during mechanical ventilation in general anesthesia: BodyVent, a randomized controlled trial

Abstract Background In patients requiring general anesthesia, lung-protective ventilation can prevent postoperative pulmonary complications, which are associated with higher morbidity, mortality, and prolonged hospital stay. Application of positive end-expiratory pressure (PEEP) is one component of lung-protective ventilation. The correct strategy for setting adequate PEEP, however, remains controversial. PEEP settings that lead to a lower pressure difference between end-inspiratory plateau pressure and end-expiratory pressure (“driving pressure,” ΔP) may reduce the risk of postoperative pulmonary complications. Preliminary data suggests that the PEEP required to prevent both end-inspiratory overdistension and end-expiratory alveolar collapse, thereby reducing ΔP, correlates positively with the body mass index (BMI) of patients, with PEEP values corresponding to approximately 1/3 of patient’s respective BMI. Thus, we hypothesize that adjusting PEEP according to patient BMI reduces ΔP and may result in less postoperative pulmonary complications. Methods Patients undergoing general anesthesia and endotracheal intubation with volume-controlled ventilation with a tidal volume of 7 ml per kg predicted body weight will be randomized and assigned to either an intervention group with PEEP adjusted according to BMI or a control group with a standardized PEEP of 5 mbar. Pre- and postoperatively, lung ultrasound will be performed to determine the lung aeration score, and hemodynamic and respiratory vital signs will be recorded for subsequent evaluation. The primary outcome is the difference in ΔP as a surrogate parameter for lung-protective ventilation. Secondary outcomes include change in lung aeration score, intraoperative occurrence of hemodynamic and respiratory events, oxygen requirements and postoperative pulmonary complications. Discussion The study results will show whether an intraoperative ventilation strategy with PEEP adjustment based on BMI has the potential of reducing the risk for postoperative pulmonary complications as an easy-to-implement intervention that does not require lengthy ventilator maneuvers nor additional equipment. Trial registration German Clinical Trials Register (DRKS), DRKS00031336. Registered 21st February 2023. Trial status The study protocol was approved by the ethics committee of the Christian-Albrechts-Universität Kiel, Germany, on 1st February 2023. Recruitment began in March 2023 and is expected to end in September 2023

Regulation of β<i>-arrestin 2</i> (<i>Arrb2</i>) mRNA in mice brain.

<p>Each PCR experiment was repeated 3 times per animal (n=6), one representative PCR result is shown (A). Values below the bands display the average level of band densities of <i>Arrb2</i> compared with those of the housekeeping gene <i>Hprt1</i> (not shown) for each group (mean ± SEM). Regulation of <i>Arrb2</i> mRNA expression in group AM, CM, LM and KM compared with group P (B). Columns show the mean upregulation or downregulation of <i>Arrb2</i> mRNA expression in group AM, CM, LM and KM compared with group P, bars denote SEM; numbers display the number of mice in each group. AM: acute morphine administration group; CM: chronic morphine administration group; LM: coadministration of morphine with clonidine group; KM: coadministration of morphine with s-ketamine group. ^#<i>P</i><0.01 compared with group P, *<i>P</i><0.01 compared with group AM.</p

Protocol of drug administration.

<p>D: day. Numbers (0.1, 5, 10, 20) display the dose of drugs in mg·kg^-1, 0 represents saline. Application was performed subcutaneously in a volume of 200-300µl thrice daily. N=6 animals per group.</p

Effect of clonidine alone and in combination with chronic morphine administration on the mechanical threshold (A) and the tail flick latency (B).

<p>Mechanical threshold and tail flick latency were evaluated daily before injection (D_-4-D₀, no significant changes compared to D₀, data not shown), during injection (D₁-D₁₄) and after injection (D₁₅-D₁₈). The grey shaded surface represents 4 days (D₁₅-D₁₈) after injection. The results are presented as %MPE ± SEM (n=6). P: placebo group; CM: chronic morphine administration group; L: clonidine administration group; LM: coadministration of morphine with clonidine group. *<i>P</i><0.05, **<i>P</i><0.01 compared with baseline; whereas ^#<i>P</i><0.001 compared with group CM.</p

Effect of s-ketamine alone and in combination with chronic morphine administration on the mechanical threshold (A) and the tail flick latency (B).

<p>Mechanical threshold and tail flick latency were evaluated daily before injection (D_-4-D₀), during injection (D₁-D₁₄) and after injection (D₁₅-D₁₈). The grey shaded surface represents 4 days (D₁₅-D₁₈) after injection. The results are presented as %MPE ± SEM (n = 6). P: placebo group; CM: chronic morphine administration group; K: s-ketamine administration group; KM: coadministration of morphine with s-ketamine group. *<i>P</i><0.05; **<i>P</i><0.01 compared with baseline; whereas ^#<i>P</i><0.01 compared with group CM.</p

Regulation of <i>NMDAR1</i> mRNA in mice brain.

<p>Each PCR experiment was repeated 3 times per animal (n=6), one representative PCR result is shown (A). Values below the bands display the average level of band densities of <i>NMDAR1</i> compared with those of the housekeeping gene <i>Hprt1</i> (not shown) for each group (mean ± SEM). Regulation of <i>NMDAR1</i> mRNA expression in group AM, CM, LM and KM compared with group P (B). Columns show the mean upregulation or downregulation of <i>NMDAR1</i> mRNA expression in group AM, CM, LM and KM compared with group P, bars denote SEM; numbers display the numbers of mice in each group. AM: acute morphine administration group; CM: chronic morphine administration group; LM: coadministration of morphine with clonidine group; KM: coadministration of morphine with s-ketamine group. ^#<i>P</i><0.05; ^##<i>P</i><0.01; ^###<i>P</i><0.001 compared with group P, *<i>P</i><0.001 compared with group AM, and ⁺<i>P</i><0.001 compared with group CM.</p

Effect of acute or chronic morphine administration on the mechanical threshold (A) and the tail flick latency (B).

<p>Mechanical threshold and tail flick latency were evaluated daily before injection (D_-4-D_0, no significant changes compared to D₀, data not shown), during injection (D₁-D₁₄) and after injection (D₁₅-D₁₈). The grey shaded surface represents 4 days after the final injection. The results are presented as % MPE ± SEM (n=6). P: placebo group; AM: acute morphine administration group; CM: chronic morphine administration group; *<i>P</i><0.05; **<i>P</i><0.01 compared with baseline; ^#<i>P</i><0.05; ^##<i>P</i><0.01 compared with group P.</p