High-PEEP Noninvasive Ventilation By Means of Mask as the Respiratory Support in COVID-19 ARDS Patients: Experience From General Hospital Slavonski Brod.

OBJECTIVE: Despite widespread use of noninvasive ventilation (NIV) in some coronavirus disease 2019 (COVID-19) hypoxemic patients, its clinical application is still subject of debate. METHODS: This is a retrospective, observational study with data collected from 91 consecutive patients treated in COVID intensive care unit (ICU) in our institution between October 2020 and February 2021. Outcomes were represented as ventilation hours, ICU and hospital length of stay, and ICU and hospital mortality. RESULTS: Patients' mean age was 66 ± 11 y and severe COVID-19 pneumonia with mean paO2/FiO2 137 ± 57 was observed in 90% of the patients. High positive end-expiratory pressure (PEEP) NIV by means of total face mask was initially applied in 58 (64%) patients, high flow oxygen therapy (HFOT) in 25 (27%) patients, whilst invasive mechanical ventilation (IMV) started at the moment of admission in 8 (9%) patients. NIV and high flow oxygen therapy (HFOT) have been kept on throughout ICU stay in 50 (55%) patients, while 41 (45%) patients were put on IMV. Overall ICU mortality was 41%, while ICU mortality of patients on NIV was 14%. CONCLUSIONS: High PEEP NIV was convenient and safe as initial respiratory support and in some COVID-19 ARDS patients remained an optimal respiratory support throughout their disease.

In relation to NO-System, Stable Pentadecapeptide BPC 157 Counteracts Lidocaine-Induced Adverse Effects in Rats and Depolarisation In Vitro.

Recently, the pentadecapeptide BPC 157-induced counteraction of bupivacaine cardiotoxicity has been reported. Medication includes (i) lidocaine-induced local anesthesia via intraplantar application and axillary and spinal (L4-L5) intrathecal block, (ii) lidocaine-induced arrhythmias, (iii) convulsions, and (iv) lidocaine-induced HEK293 cell depolarisation. BPC 157 applications (intraplantar, intraperitoneal, and intragastric) were given (i) immediately after lidocaine, (ii) 10 min after, or (iii) 5 min before. The BPC 157/NO-system relationship was verified with NO-agents, the NOS-blocker L-NAME and the NOS-substrate L-arginine, given alone and/or together, in axillary and spinal intrathecal blocks. BPC 157 applied immediately after lidocaine or 5 min before the application of lidocaine considerably ameliorated plantar presentation. BPC 157 medication considerably counteracted lidocaine-induced limb function failure; L-NAME was counteracted; L-arginine exhibited counteraction when given immediately after lidocaine, but prolongation was seen when given later. Given together, prophylactically or therapeutically, L-NAME and L-arginine (L-NAME + L-arginine) counteracted the other's response. BPC 157 maintained its original response when given together with L-NAME or L-arginine. When BPC 157 was given together with L-NAME and L-arginine, its original response reappeared. BPC 157 antagonised the lidocaine-induced bradycardia and eliminated tonic-clonic convulsions. Also, BPC 157 counteracted the lidocaine-induced depolarisation of HEK293 cells. Thus, BPC 157 has antidote activity in its own right against lidocaine and local anesthetics.

Pentadecapeptide BPC 157 resolves Pringle maneuver in rats, both ischemia and reperfusion.

BACKGROUND: The Pringle maneuver [portal triad obstruction(PTO)] provides huge disturbances during ischemia and even more thereafter in reperfusion. Contrarily, a possible solution may be stable gastric pentadecapeptide BPC 157, with already documented beneficial effects in ischemia/reperfusion conditions. Recently, BPC 157, as a cytoprotective agent, successfully resolved vessel occlusions in rats (ischemic colitis; deep vein thrombosis, superior anterior pancreaticoduodenal vein; bile duct cirrhosis) through rapid collateral vessel recruitment to circumvent vessel occlusion. Thereby, medication BPC 157 regimens were administered as a single challenge before and during ischemia or, alternatively, at various time points during reperfusion. AIM: To introduce BPC 157 therapy against pringle maneuver-damage. METHODS: In deeply anesthetised rats, the portal triad was clamped up for 30 min. Rats then underwent reperfusion for either 15 min or 24 h. Medication [(10 µg, 10 ng/kg) regimens, administered as a single challenge] picked (a) ischemia, PTO period [at 5 min before (ip) or at 5 or 30 min of ligation time (as a bath to PTO)] or (b) reperfusion, post-PTO period [at 1 or 15 min (bath during surgery) or 24 h (ip) reperfusion-time]. We provided gross, microscopy, malondialdehyde, serum enzymes, electrocardiogram, portal, caval, and aortal pressure, thrombosis and venography assessments. RESULTS: BPC 157 counteracts electrocardiogram disturbances (increased P wave amplitude, S1Q3T3 QRS pattern and tachycardia). Rapidly presented vascular pathway (portal vein-superior mesenteric vein-inferior mesenteric vein-rectal veins-left ileal vein-inferior caval vein) as the adequate shunting immediately affected disturbed haemodynamics. Portal hypertension and severe aortal hypotension during PTO, as well as portal and caval hypertension and mild aortal hypotension in reperfusion and refractory ascites formation were markedly attenuated (during PTO) or completely abrogated (reperfusion); thrombosis in portal vein tributaries and inferior caval vein or hepatic artery was counteracted during portal triad obstruction PTO. Also, counteraction included the whole vicious injurious circle [i.e., lung pathology (severe capillary congestion), liver (dilated central veins and terminal portal venules), intestine (substantial capillary congestion, submucosal oedema, loss of villous architecture), splenomegaly, right heart (picked P wave values)] regularly perpetuated in ischemia and progressed by reperfusion in Pringle rats. CONCLUSION: BPC 157 resolves pringle maneuver-damage in rats, both for ischemia and reperfusion.

Fistulas Healing. Stable Gastric Pentadecapeptide BPC 157 Therapy.

This review is focused on the healing of fistulas and stable gastric pentadecapeptide BPC 157. Assuming that the healing of the various wounds is essential also for the gastrointestinal fistulas healing, the healing effect on fistulas in rats, consistently noted with the stable gastric pentadecapeptide BPC 157, may raise several interesting possibilities. BPC 157 is originally an anti-ulcer agent, native to and stable in human gastric juice (for more than 24 h). Likely, it is a novel mediator of Robert's cytoprotection maintaining gastrointestinal mucosal integrity. Namely, it is effective in the whole gastrointestinal tract, and heals various wounds (i.e., skin, muscle, tendon, ligament, bone; ulcers in the entire gastrointestinal tract; corneal ulcer); LD1 is not achieved. It is used in ulcerative colitis clinical trials, and now in multiple sclerosis, and addressed in several reviews. Therefore, it is not surprising that BPC 157 has documented consistent healing of the various gastrointestinal fistulas, external (esophagocutaneous, gastrocutaneous, duodenocutaneous, colocutaneous) and internal (colovesical, rectovaginal). Taking fistulas as a pathological connection, this rescue is verified with the beneficial effects in rats with the various gastrointestinal anastomoses, esophagogastric, jejunoileal, colo-colonic, ileoileal, esophagojejunal, esophagoduodenal, and gastrojejunal. This beneficial effect occurs equally when the gastrointestinal anastomoses are impaired with the application of NSAIDs, cysteamine, large bowel resection, as well as concomitant esophageal, gastric, and duodenal lesions and/or ulcerative colitis presentation, short bowel syndrome progression, liver and brain disturbances presentation. Particular aspects of the BPC 157 healing of the fistulas are especially emphasized.

Pentadecapeptide BPC 157 shortens duration of tetracaine- and oxybuprocaine-induced corneal anesthesia in rats.

We focused on the relationship of 0.5% tetracaine- and 0.4% oxybuprocaine-induced corneal anesthesia in rats, and pentadecapeptide BPC 157 (0.4 µg/eye), along with nitric oxide synthase (NOS) inhibitor N(gamma)-nitro-L-arginine methyl ester (L-NAME) (0.1 mg/eye) and/or NOS substrate L-arginine (2 mg/eye), applied in the form of eye drops. We assessed corneal sensitivity recovery (Cochet-Bonnet esthesiometer), corneal lesion elimination (staining with 10% fluorescein) and decrease in tear volume (Schirmer test). BPC 157 administration had a full counteracting effect. Recovery also occurred in the presence of NOS blockade and NOS substrate application. L-arginine eventually shortened duration of corneal insensitivity and exerted corneal lesion counteraction (and counteraction of tetracaine-induced decrease of tear volume) only in earlier but not in later period. L-NAME application led to longer duration of corneal insensitivity, increase in corneal lesions and decrease in tear volume. When L-NAME and L-arginine were applied together, they antagonized each other's effect. These distinctions may indicate particular NOS involvement (corneal insensitivity vs. corneal lesion along with tear production), distinctively affected by the administration of NO agents. However, additional BPC 157 co-administration would re-establish counteraction over topical ophthalmic anesthetic-induced effect, be it in its early or late course. We suggest BPC 157 as an antidote to topical ophthalmic anesthetics.

Chronic obstructive pulmonary disease and weaning of difficult-to-wean patients from mechanical ventilation: randomized prospective study.

AIM: To compare T-tube and pressure support ventilation (PSV) as two methods of mechanical ventilation weaning of patients with chronic obstructive pulmonary disease (COPD) after failed extubation. METHODS: A prospective randomized trial carried out at the multidisciplinary intensive care unit (ICU) over 2 years included 136 patients with COPD who required mechanical ventilation longer than 24 hours. The patients who could be weaned from mechanical ventilation were randomized to either a T-tube or PSV 2-hour spontaneous breathing trial. The patients in whom 2-hour trial was successful were extubated and excluded from further research. Patients in whom 2-hour trial failed had mechanical ventilation reinstated and underwent the same weaning procedure after 24 hours in case they fulfilled the weaning criteria. The weaning outcome was assessed according to the following parameters: extubation success, mechanical ventilation duration, time spent in ICU, reintubation rate, and mortality rate. RESULTS: Two-hour trial failed in 31 patients in T-tube and 32 patients in PSV group, of whom 17 and 23, respectively, were successfully extubated (P<0.001, chi(2)test). Mechanical ventilation lasted significantly longer in T-tube than in PSV group (187 hours vs 163 hours, respectively, P<0.001, Mann-Whitney test). Also, patients in T-tube group spent significantly more time in ICU than patients in PVS group (241 hours [interquartile range 211-268] vs 210 hours [211-268], respectively, P<0.001, Mann-Whitney test). Reintubation was required in 8 and 6 patients in T-tube and PVS group, respectively, and death occurred in 4 and 2 patients, respectively, during ICU stay. CONCLUSION: Patients with COPD who failed the 2-hour spontaneous breathing trial had more favorable outcome when PVS rather than T-tube method was used for weaning from mechanical ventilation.