The Effect of Epidural Analgesia on Quality of Recovery (QoR) after Open Radical Nephrectomy: Randomized, Prospective, and Controlled Trial.

No studies are currently evaluating the quality of recovery (QoR) after open radical nephrectomy (ORN) and epidural morphine analgesia. This was a randomized, prospective, and controlled study that explored the QoR on the first postoperative day after ORN. Eighty subjects were randomized into two groups. The first group received general anesthesia combined with epidural anesthesia and postoperative epidural analgesia with morphine and ropivacaine. The second group received general anesthesia and continuous postoperative intravenous analgesia with tramadol. Both groups received multimodal analgesia with metamizole. The primary outcome measure was the total QoR-40 score. The secondary outcome measures were QoR-15, QoR-VAS, and the visual analog scale (VAS) for pain, anxiety, and nausea. The median difference in the QoR-40 score after 24 postoperative hours between the two groups of patients was 10 (95% CI: 15 to 5), p < 0.0001. The median score and IQR of QoR-40 during the first 24 postoperative hours in the epidural group was 180 (9.5), and in the control group, it was 170 (13). The general independence test for secondary outcomes between groups was significant (p < 0.01). QoR-VAS was correlated with QoR-40 (r = 0.63, p ≤ 0.001) and with QoR-15 (r = 0.54, p ≤ 0.001). The total QoR-40 and QoR-15 alpha coefficients with a 95% CI were 0.88 (0.85-0.92) and 0.73 (0.64-0.81), respectively. There was a significant difference in the QoR between the epidural and the control groups after ORN. The QoR-40 and QoR-15 showed good convergent validity and reliability.

Barotrauma in patients with severe coronavirus disease 2019-retrospective observational study.

Background: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Although it is known that the COVID-19 acute respiratory distress syndrome (ARDS) is associated with higher incidence of pulmonary barotrauma, unique mechanisms causing the aforementioned complication are still to be investigated. The goal of this research was to investigate the incidence of barotrauma among COVID-19 patients treated in the intensive care unit (ICU) and to examine different clinical outcomes among those subjects. Methods: This retrospective observational cohort study included adult COVID-19 patients admitted to ICU from September 1, 2020, to February 28, 2022. All admitted subjects received invasive respiratory support. Subjects were divided into two groups based on occurrence of pulmonary barotrauma. Data were collected from available electronical medical records. Results: In the study period, a total of 900 subjects met inclusion criteria. Pulmonary barotrauma occurred in 88 (9.8%) of them. Subcutaneous emphysema developed in 73 (83%), pneumomediastinum in 68 (77.3%) and pneumothorax in 54 (61.4%) subjects. A small group of subjects developed less common complications like pneumoperitoneum (8 subjects, 9.1%) and pneumopericardium (2 subjects, 2.3%). Survival rate was higher in control than in barotrauma group [396 (48.8%) vs. 22 (25.0%), P<0.05]. There was also a significant difference between two groups in PaO2/FiO2 ratio on admission, duration of non-invasive respiratory support before mechanical ventilation, duration of mechanical ventilation and duration of ICU and hospital stay, all in favour of control group. Conclusions: Development of barotrauma in patients with severe forms of COVID-19 disease and in need of respiratory support is associated with longer ICU and hospital stay as well as lower survival rates at hospital discharge. Further efforts are needed in understanding mechanism in developing barotrauma and finding new prevention and treatment options.

Vitamin D Supplementation and Clinical Outcomes in Severe COVID-19 Patients-Randomized Controlled Trial.

COVID-19 symptoms vary from asymptomatic cases to moderate and severe illness with patients needing hospitalization and intensive care treatment. Vitamin D is associated with severity of viral infections and has an immune-modulatory effect in immune response. Observational studies showed a negative association of low vitamin D levels and COVID-19 severity and mortality outcomes. In this study, we aimed to determine whether daily supplementation of vitamin D during intensive care unit (ICU) stay in COVID-19 patients with severe illness affects clinically relevant outcomes. Patients with COVID-19 disease in need of respiratory support admitted to the ICU were eligible for inclusion. Patients with low vitamin D levels were randomized into one of two groups: the intervention group received daily supplementation of vitamin D and the control group did not receive vitamin D supplementation. In total, 155 patients were randomized: 78 into the intervention group and 77 into the control group. There was no statistically significant difference in number of days spent on respiratory support, although the trial was underpowered for the main outcome. There was no difference in any of the secondary outcomes analyzed between two groups. Our study suggests no benefit in vitamin D supplementation to patients with severe COVID-19 disease admitted to the ICU and in need of respiratory support in any of the analyzed outcomes.

Health-Related Quality of Life of COVID-19 Survivors Treated in Intensive Care Unit-Prospective Observational Study.

Purpose: To investigate the quality of life (QoL) of survivors from severe forms of COVID-19 treated in the ICU. Methods: In this study, we investigated the QoL of patients with severe COVID-19 treated in the ICU from November 2021 to February 2022. In the study period, 288 patients were treated in ICU and 162 were alive at the time of analysis. Of those, 113 patients were included in this study. QoL was analyzed 4 months after ICU admission using the EQ-5D-5L questionnaire administered by telephone. Results: Of the 162 surviving patients, 46% reported moderate to severe problems in the anxiety/depression domain, 37% had moderate to severe problems in usual activities, and 29% in the mobility domain. Older patients had lower QoL in mobility, self-care and usual activities domains. Female patients had lower QoL in usual activities, while male patients had lower QoL in the self-care domain. Patients who spent longer time on invasive respiratory support and those with longer hospital lengths of stay had lower QoL in all domains. Conclusion: Severe COVID-19 reduces HRQoL in a significant number of survivors 4 months after ICU admission. Early recognition of patients at increased risk for reduced QoL could lead to early focused rehabilitation and improved QoL of these patients.

Midazolam versus Dexmedetomidine in Patients at Risk of Obstructive Sleep Apnea during Urology Procedures: A Randomized Controlled Trial.

Benzodiazepines are the most commonly used sedatives for the reduction of patient anxiety. However, they have adverse intraoperative effects, especially in obstructive sleep apnea (OSA) patients. This study aimed to compare dexmedetomidine (DEX) and midazolam (MDZ) sedation considering intraoperative complications during transurethral resections of the bladder and prostate regarding the risk for OSA. This study was a blinded randomized clinical trial, which included 115 adult patients with a mean age of 65 undergoing urological procedures. Patients were divided into four groups regarding OSA risk (low to medium and high) and choice of either MDZ or DEX. The doses were titrated to reach a Ramsay sedation scale score of 4/5. The intraoperative complications were recorded. Incidence rates of desaturations (44% vs. 12.7%, p = 0.0001), snoring (76% vs. 49%, p = 0.0008), restlessness (26.7% vs. 1.8%, p = 0.0044), and coughing (42.1% vs. 14.5%, p = 0.0001) were higher in the MDZ group compared with DEX, independently of OSA risk. Having a high risk for OSA increased the incidence rates of desaturation (51.2% vs. 15.7%, p < 0.0001) and snoring (90% vs. 47.1%, p < 0.0001), regardless of the sedative choice. DEX produced fewer intraoperative complications over MDZ during sedation in both low to medium risk and high-risk OSA patients.

BPC 157, L-NAME, L-Arginine, NO-Relation, in the Suited Rat Ketamine Models Resembling "Negative-Like" Symptoms of Schizophrenia.

We attempted throughout the NO-system to achieve the particular counteraction of the ketamine-induced resembling "negative-like" schizophrenia symptoms in rats using pentadecapeptide BPC 157, and NO-agents, NG-nitro-L-arginine methylester (L-NAME), and/or L-arginine, triple application. This might be the find out the NO-system organized therapy (i.e., simultaneously implied NO-system blockade (L-NAME) vs. NO-system over-stimulation (L-arginine) vs. NO-system immobilization (L-NAME+L-arginine)). The ketamine regimen (intraperitoneally/kg) included: 3 mg (cognitive dysfunction, novel object recognition test), 30 mg (anxiogenic effect (open field test) and anhedonia (sucrose test)), and 8 mg/3 days (social withdrawal). Medication (mg/kg intraperitoneally) was L-NAME (5), L-arginine (100), and BPC 157 (0.01), alone and/or together, given immediately before ketamine (L-NAME, L-arginine, and combination) or given immediately after (BPC 157 and combinations). BPC 157 counteracted ketamine-cognition dysfunction, social withdrawal, and anhedonia, and exerted additional anxiolytic effect. L-NAME (antagonization, social withdrawal) and L-arginine (antagonization, cognitive dysfunction, anhedonia) both included worsening cognitive dysfunction, anhedonia, and anxiogenic effect (L-NAME), social withdrawal, and anxiogenic effect (L-arginine). Thus, ketamine-induced resembling "negative-like" schizophrenia symptoms were "L-NAME non-responsive, L-arginine responsive" (cognition dysfunction), "L-NAME responsive, L-arginine non-responsive" (social withdrawal), "L-NAME responsive, L-arginine responsive, opposite effect" (anhedonia) and "L-NAME responsive, L-arginine responsive, parallel effect" (both anxiogening). In cognition dysfunction, BPC 157 overwhelmed NO-agents effects. The mRNA expression studies in brain tissue evidenced considerable overlapping of gene overexpression in healthy rats treated with ketamine or BPC 157. With the BPC 157 therapy applied immediately after ketamine, the effect on Nos1, Nos2, Plcg1, Prkcg, and Ptgs2 (increased or decreased expression), appeared as a timely specific BPC 157 effect on ketamine-specific targets.

Effects of Different Inhalation Therapy on Ventilator-Associated Pneumonia in Ventilated COVID-19 Patients: A Randomized Controlled Trial.

The effect of routine inhalation therapy on ventilator-associated pneumonia (VAP) in mechanically ventilated patients with the coronavirus disease (COVID-19) has not been well-defined. This randomized controlled trial included 175 eligible adult patients with COVID-19 who were treated with mechanical ventilation at the University Hospital of Split between October 2020 and June 2021. Patients were randomized and allocated to a control group (no routine inhalation) or one of the treatment arms (inhalation of N-acetylcysteine; 5% saline solution; or 8.4% sodium bicarbonate). The primary outcome was the incidence of VAP, while secondary outcomes included all-cause mortality. Routine inhalation therapy had no effect on the incidence of bacterial or fungal VAP nor on all-cause mortality (p > 0.05). Secondary analyses revealed a significant reduction of Gram-positive and methicillin-resistant Staphylococcus aureus (MRSA) VAP in the treatment groups. Specifically, the bicarbonate group had a statistically significantly lower incidence of Gram-positive bacterial VAP (4.8%), followed by the N-acetylcysteine group (10.3%), 5% saline group (19.0%), and control group (34.6%; p = 0.001). This difference was driven by a lower incidence of MRSA VAP in the bicarbonate group (2.4%), followed by the N-acetylcysteine group (7.7%), 5% saline group (14.3%), and control group (34.6%; p < 0.001). Longer duration of ventilator therapy was the only significant, independent predictor of any bacterial or fungal VAP in the multivariate analysis (aOR 1.14, 95% CI 1.01−1.29, p = 0.038 and aOR 1.05, 95% CI 1.01−1.10, p = 0.028, respectively). In conclusion, inhalation therapy had no effect on the overall VAP incidence or all-cause mortality. Further studies should explore the secondary findings of this study such as the reduction of Gram-positive or MRSA-caused VAP in treated patients.

The Effect of Epidural Analgesia on Quality of Recovery (QoR) after Radical Prostatectomy.

No studies are currently regarding the quality of recovery (QoR) after open radical prostatectomy (ORP) and epidural morphine analgesia. This was a randomized, prospective, and controlled study that explored QoR on the first postoperative day after ORP. Sixty-one men were randomized into two groups. The first (epidural) group received general anesthesia combined with epidural anesthesia and postoperative epidural analgesia with morphine and ropivacaine. The second (control) group received general anesthesia and continuous postoperative intravenous analgesia with tramadol. Both groups received multimodal analgesia with metamizole. The primary outcome measure was the total QoR-40 score. Secondary outcome measures were: QoR-15, QoR-VAS and the visual analogue scale (VAS) for pain, anxiety and nausea. The median difference in the total QoR-40 score after 24 postoperative hours between the two groups of patients was 2 (95% CI: −3 to 8), p = 0.35. The global multivariate inference test for secondary outcomes between groups was not significant p > 0.05). QoR-VAS was correlated with QoR-40 (r = 0.69, p ≤ 0.001) and with QoR-15 (r = 0.65, p ≤ 0.001). The total QoR-40 and QoR-15 alpha coefficient with 95% CI was 0.88 (0.83-0.92) and 0.83 (0.77−0.89), respectively. There was no difference in the QoR between the epidural and the control group after ORP. The QoR-40 and QoR-15 showed good convergent validity and adequate reliability.

Stable Gastric Pentadecapeptide BPC 157 Heals Established Vesicovaginal Fistula and Counteracts Stone Formation in Rats.

With the stable gastric pentadecapeptide BPC 157 therapy known to heal various both external and internal rat fistulas, we attempt to approach vesicovaginal fistula, continuous urine leaking through vagina, bladder stones, and a possible therapy solution among rats with well-formed 2 week-fistulas (vaginal/vesical 4 mm large defects) started with delayed therapy. Subsequent control fistula course (the subsequent 1, 2, 4, and 6 weeks) since beginning revealed the failed healing, fistula leaking, adhesions, urinary leaking through vagina, failed epithelization, collagenization, granulation tissue and neovascularization, increased inflammation, and necrosis. Thereby, the later intervals revealed the persistent inability to sustain even minimal volume, vesical, and vaginal defects and stone formation at the end of the experiment (fistula-time day 56). BPC 157 therapy (10 µg/kg, 10 ng/kg, intraperitoneally once time daily or perorally in drinking water until sacrifice) was initiated with a considerable delay (at 2 weeks after fistula formation). Already within 1 week therapy, all BPC 157 regimens stopped urinary leaking through vagina, reversed the otherwise resistant poor healing course to the increased epithelization, collagenization, granulation tissue and neovascularization, decreased inflammation, and decreased necrosis. Thereby, at later intervals, all BPC 157 rats exhibited a five times larger volume that can be sustained before leaking as in healthy, vesical, and vaginal defects completely closed and no stone formation. Thus, macro/microscopic and functional recovery, and counteracted stone formation. Concluding, BPC 157 therapy's beneficial effects resulted in healing and no stone formation, with µg- and ng-regimens, either given daily perorally in drinking water or intraperitoneally.

BPC 157: The counteraction of succinylcholine, hyperkalemia, and arrhythmias.

After the demonstration of its life-saving effect in severe hyperkalemia and the recovery of skeletal muscle after injury, pentadecapeptide BPC 157 has been shown to attenuate the local paralytic effect induced by succinylcholine, in addition to systemic muscle disability (and consequent muscle damage). Hyperkalemia, arrhythmias and a rise in serum enzyme values, were counteracted in rats. Assessments were made at 3 and 30min and 1, 3, 5, and 7 days after succinylcholine administration (1.0mg/kg into the right anterior tibial muscle). BPC 157 (10µg/kg, 10ng/kg) (given intraperitoneally 30min before or immediately after succinylcholine or per-orally in drinking water through 24h until succinylcholine administration) mitigated both local and systemic disturbances. BPC 157 completely eliminated hyperkalemia and arrhythmias, markedly attenuated or erradicated behavioral agitation, muscle twitches, motionless resting and completely eliminated post-succinylcholine hyperalgesia. BPC 157 immediately eliminated leg contractures and counteracted both edema and the decrease in muscle fibers in the diaphragm and injected/non-injected anterior tibial muscles. Therefore, the depolarizing neuromuscular blocker effects of succinylcholine were successfully antagonized.

Pentadecapeptide BPC 157 and anaphylactoid reaction in rats and mice after intravenous dextran and white egg administration.

Anesthetized mice or rats received intravenously 6%, 10%, 20%, 40%, 60%, 80%, and 90% dextran and/or white egg (1ml/rat or 0.15ml/mouse) into their tails. Medication (/kg b.w., 5ml/kg) was given intraperitoneally (BPC 157 10µg, 1µg, 10ng, and 10pg/kg, chloropyramine 20mg/kg, and cimetidine 10mg/kg intraperitoneally, alone or in combination while controls received an equivolume of saline), immediately after challenge or, alternatively, at 5min after or 24 or 48h before challenge. The effect was assessed at 5, 10, 20 and 30min after dextran and/or white egg challenge. We commonly noted prominent edema involving the face, upper and lower lip, snout, paws and scrotum (presented with extreme cyanosis), poor respiration and the number of fatalities after dextran and/or white egg application. Contrary, BPC 157 regimens (10µg, 1µg, 10ng, and 10pg/kg) effectively, may both prevent anaphylactoid reactions that may arise from dextran and/or white egg application and furthermore, rescue already advanced reactions when given after the challenge. Chloropyramine and cimetidine given alone were only moderately effective. When given together with BPC 157, the observed effect correlates with the strong effect of BPC 157 given alone.