Acutely increased aquaporin-4 exhibits more potent protective effects in the cortex against single and repeated isoflurane-induced neurotoxicity in the developing rat brain.

Damage to hippocampus, cerebellum, and cortex associated with cognitive functions due to anesthetic-induced toxicity early in life may cause cognitive decline later. Aquaporin 4 (AQP4), a key protein in waste clearance pathway of brain, is involved in synaptic plasticity and neurocognition. We investigated the effects of single and repeated isoflurane (Iso) anesthesia on AQP4 levels and brain damage. Postnatal-day (P)7 Wistar albino rats were randomly assigned to Iso or Control (C) groups. For single-exposure, pups were exposed to 1.5% Iso in 30% oxygenated-air for 3-h at P7 (Iso1). For repeated-exposure, pups were exposed to Iso for 3 days, 3-h each day, at 1-day intervals (P7 + 9 + 11) starting at P7 (Iso3). C1 and C3 groups received only 30% oxygenated-air. Based on HE-staining and immunoblotting (Bax/Bcl-2, cleaved-caspase3 and PARP1) analyses, Iso exposures caused a higher degree of apoptosis in hippocampus. Anesthesia increased 4-hydroxynonenal (4HNE), oxidative stress marker; the highest ROS accumulation was determined in cerebellum. Increased inflammation (TNF-α, NF-κB) was detected. Multiple Iso-exposures caused more significant damage than single exposure. Moreover, 4HNE and TNF-α contributed synergistically to Iso-induced neurotoxicity. After anesthesia, higher expression of AQP4 was detected in cortex than hippocampus and cerebellum. There was an inverse correlation between increased AQP4 levels and apoptosis/ROS/inflammation. Correlation analysis indicated that AQP4 had a more substantial protective profile against oxidative stress than apoptosis. Remarkably, acutely increased AQP4 against Iso exhibited a more potent neuroprotective effect in cortex, especially frontal cortex. These findings promote further research to understand better the mechanisms underlying anesthesia-induced toxicity in the developing brain.

Mild Hypothermia via External Cooling Improves Lung Function and Alleviates Pulmonary Inflammatory Response and Damage in Two-Hit Rabbit Model of Acute Lung Injury.

OBJECTIVES: Targeted temperature management (TTM) with therapeutic hypothermia (TH) has an organ-protective effect by mainly reducing inflammatory response. Here, our objective was to determine, for the first time, whether mild TH with external cooling, a simple and inexpensive method, could be safe or even beneficial in two-hit rabbit model of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). METHODS: Twenty-two New Zealand rabbits (6-month-old) were randomly divided into healthy control (HC) with conventional ventilation, but without injury, model group (ALI), and hypothermia group with external cooling (ALI-HT). After induction of ALI/ARDS through mild lung-lavages followed by non-protective ventilation, mild hypothermia was started in ALI-HT group (body temperature of 33-34 °C). All rabbits were conventionally ventilated for an additional 6-h by recording respiratory parameters. Finally, lung histopathology and inflammatory response were evaluated. RESULTS: Hypothermia was associated with higher oxygen saturation, resulting in partial improvement in the P/F ratio (PaO2/FiO2), oxygenation index, mean airway pressure, and PaCO2, but did not affect lactate levels. The ALI-HT group had lower histopathological injury scores (hyperemia, edema, emphysema, atelectasis, and PMN infiltration). Further, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6 and -8 levels in lung tissue and serum samples markedly reduced due to hypothermia. CONCLUSION: Mild TH with external cooling reduced lung inflammation and damage, whereas it resulted in partial improvement in gas exchanges. Our findings highlight that body temperature control may be a potentially supportive therapeutic option for regulating cytokine production and respiratory parameters in ALI/ARDS.

Continuous Endotracheal Tube Cuff Pressure Control Decreases Incidence of Ventilator-Associated Pneumonia in Patients with Traumatic Brain Injury.

BACKGROUND: Ventilator-associated pneumonia (VAP) is a common cause of morbidity and mortality in intensive care unit (ICU), and among the several preventative strategies described to reduce the incidence of VAP, the most important is the endotracheal tube cuff (ETC) pressure. The present study was conducted on 60 patients who required mechanical ventilation (MV) in the ICU with traumatic brain injury (TBI). METHODS: The patients were randomized into two groups of 30, in which ETC pressure was regulated using a smart cuff manager (SCM) (Group II), or manual measurement approach (MMA) (Group I). Demographic data, MV duration, length of ICU stay and mortality rates were recorded. The clinical pulmonary infection scores (CPISs), C-reactive protein (CRP) values, and the fraction of inspired oxygen (FiO2) and positive end-expiratory pressure (PEEP) values of the groups were compared at baseline, and at hours 48, 72 and 96. RESULTS: In Group I, CPIS values significantly higher than Group II in 48th, 72nd and 96th hours (p < 0.05). In Group I, PEEP values and deep tracheal aspirate (DTA) culture growth rates significantly higher than Group II in 72nd and 96th hours (p < 0.05). CONCLUSION: The continuous maintenance of ETC pressure using SCM reduced the incidence of VAP.

Reverse Trendelenburg position applied prior to pneumoperitoneum prevents excessive increase in optic nerve sheath diameter in laparoscopic cholecystectomy: randomized controlled trial.

The aim of this randomized controlled trial was to determine whether applying the reverse Trendelenburg position before pneumoperitoneum has a preventive effect on increased intracranial pressure using optic nerve sheath diameter (ONSD) measurement as a noninvasive parameter. Seventy-nine patients were allocated to two groups according to whether pneumoperitoneum was applied in the supine position (group S, n = 40) or in the reverse Trendelenburg position (group RT, n = 39). The ONSD was measured at the following time points: T0: before anesthesia; T1: after endotracheal intubation; T2: after pneumoperitoneum in group S and after positioning in group RT; T3: after positioning in group S and after pneumoperitoneum in group RT; T4: 30 min after endotracheal intubation, and T5: after desufflation. The end-tidal carbon dioxide (EtCO2), regional cerebral oxygen saturation (rSO2), peripheral oxygen saturation (SpO2), mean arterial pressure (MAP), heart rate (HR), peak inspiratory pressure (Ppeak), and dynamic compliance (Cdyn) were recorded. Background and perioperative characteristics were similar in both groups. In group S, the ONSD was higher at T2, T3, T4, and T5 than that in group RT (p < 0.001, p = 0.002, p = 0.001, and p = 0.012, respectively). In the same group, the number of patients with an ONSD above 5.8 mm was higher at T2, T3, and T4 (p < 0.001, p = 0.042, p = 0.036, respectively). The rSO2 and SpO2 were not different between the groups. The mean arterial pressure was lower in group RT at T2, and the HR was not different between the groups (p < 0.001). In group S, Ppeak was higher and Cdyn was lower at T2 (p < 0.001). The number of patients with nausea was higher in group S (p = 0.027). The present study demonstrates that applying the reverse Trendelenburg position before pneumoperitoneum prevented an increase in the ONSD in patients undergoing laparoscopic cholecystectomy.Trial registration The trial was registered prior to patient enrollment at https://register.clinicaltrials.gov (NCT04224532, Date of the registration: January 8, 2020).