Evaluation of personalized methylprednisolone therapy in critically ill COVID-19 patients: an observational comparative study using real-life data.

OBJECTIVE: Methylprednisolone is commonly used to attenuate the cytokine storm and prevent mortality in COVID-19 pneumonia. However, the optimal methylprednisolone dose and duration are unclear. Additional data are required on the effectiveness of methylprednisolone in reducing mortality in COVID-19. This real-life retrospective study aimed to analyze the data of a COVID-19 dedicated ICU and compare the mortality rates of standard care, low-dose, and pulse-dose methylprednisolone in patients requiring mechanical ventilatory support. PATIENTS AND METHODS: Methylprednisolone's indication, dose, and duration were determined according to the severity of COVID-19 pneumonia based on the patient's demographic parameters, comorbidities, laboratory data, radiology, and arterial blood gas analysis results. 867 patients were grouped as: no methylprednisolone (standard care), low-dose (0.5-1 mg/kg/day) methylprednisolone or pulse-dose (250-1,000 mg/day) methylprednisolone. RESULTS: The overall mortality rate was 63.78%. Adjusting the dose of methylprednisolone according to the severity of the disease resulted in statistically similar mortality rates despite the increase in disease severity. Mortality was 62.71% in standard treatment, 65.76% in low-dose, and 62.10% in pulse-dose methylprednisolone groups (p = 0.633). Invasive mechanical ventilation at admission was associated with increased mortality (HR: 1.826 [95% CI: 1.542-2.161]; p < 0.001). Hematologic disorders and malignancies, arterial blood pH and HCO3, neutrophil count, and NLR at admission were also associated with mortality. CONCLUSIONS: Personalizing the dose and duration of methylprednisolone according to the patient's disease severity assessed with demographic, clinical, and laboratory results may benefit mortality in severe COVID-19 patients receiving ventilatory support in the ICU. Hematologic disorders and malignancies, arterial blood pH and HCO3, neutrophil count, and NLR at admission were associated with mortality in our patient cohort.

The reversing effect of ondansetron on bupivacaine-induced sciatic nerve block.

Background and Aims: This experimental study was designed to test the hypothesis that ondansetron, a selective 5-HT3 receptor antagonist, would decrease the duration of motor, sensory, and proprioception blockade in a dose-dependent fashion in a bupivacaine-induced sciatic nerve blockade. Materials and Methods: Forty-nine male Wistar Albino rats who underwent unilateral sciatic nerve block were divided into seven groups with an equal number in each group. Group B: only perineural block (PB), Group BO200: PB and perineural 200 µg ondansetron, Group BO400: PB and perineural 400 µg ondansetron, Group BO800: PB and perineural 800 µg ondansetron, Group BO800IP: PB and intraperitoneal 800 µg ondansetron, Group O800: only perineural 800 µg ondansetron, Group S: sham-operated. The rats' motor, sensory, and proprioception functions were evaluated by a blinded investigator every 10 min until they returned to normal function. The recovery times of the motor, sensory, and proprioception functions were recorded and compared. All sciatic nerves were removed and examined by electron microscopy for neurotoxic signs. Results: In which sciatic nerve block was formed with bupivacaine, the duration of the motor, sensory, and proprioception functions blockade was decreased, and the duration to return to normal functions was significantly shortened at Group BO800 (p < 0.05). According to electron microscopy results, perineural 200 µg, 400 µg, and 800 µg ondansetron were not neurotoxic. Conclusion: This is the first study showing that perineural ondansetron administration (800 µg dose) reverses the effect of the local anesthetics and shortens the duration of the motor, sensory, and proprioception functions blockade.

In vitro vasoactive effects of dexmedetomidine on isolated human umbilical arteries.

OBJECTIVE: We aimed to investigate the vasoactive effects of dexmedetomidine on isolated human umbilical arteries and possible mechanisms involved. METHODS: Human umbilical artery strips were suspended in Krebs-Henseleit solution and dose-response curves were obtained for cumulative dexmedetomidine before and after incubation with different agents; propranolol, atropine, yohimbine, prazosin, indomethacin, verapamil. Effects of calcium on cumulative dexmedetomidine-induced contractions were also studied. RESULTS: Cumulative dexmedetomidine resulted in dose dependent contraction responses. Incubation with propranolol (Emax: 93.3 ± 3.26 %), atropine (Emax: 92.0 ± 6.54 %), or indomethacin (Emax: 94.25 ± 2.62 %), did not attenuate dexmedetomidine-elicited contractions (p > 0.05). There were significant decreases in the contraction responses of cumulative dexmedetomidine with yohimbine (Emax: 12.1 ± 11.9 %), prazosin (Emax: 28.8 ± 4.6 %) and verapamil (Emax: 11.2 ± 13.6 %) (p < 0.05). In Ca+2 free medium contraction responses to cumulative dexmedetomidine was insignificant (Emax: 5.20 ± 3.42 %). Addition of cumulative calcium to the Ca+2 free medium resulted in concentration dependent increase in contractions (Emax: 64.83 ± 37.7 %) (p < 0.05). CONCLUSION: Dexmedetomidine induces vasoconstriction in endothelial-free umbilical arteries via both, α1- and α2-adrenergic receptors and also extracellular Ca+2 concentrations play a major role. ß-adrenergic receptors, muscarinic cholinergic receptors, and inhibition of cyclooxygenase enzyme are not involved in this vasoconstriction (Fig. 3, Ref. 36).

Does preoperative administration of allopurinol protect the lungs from ischemia-reperfusion injury occuring during cardiopulmonary bypass?

BACKGROUND: It is investigated whether preoperative allopurinol administration protects lung injury induced by cardiopulmonary bypass (CPB). METHODS: Sixty patients with coronary artery disease who need elective coronary artery bypass grafting operations by using CPB were taken into this study. They were divided into two groups; control and allopurinol. Allopurinol (300 mg/day) was administered to the latter group during the preoperative period of 5 days. Standard CPB procedures were used in all cases. Blood was sampled for TNF-alpha, IL-6, IL-8, IL-10 before anesthesia (T0), after anesthesia and before skin incision (T1), before CPB (T2), after aortic declamping (T3), at the end of CPB (T4), 6 hours after operation (T5), 12 hours after operation (T6), and 24 hours after operation (T7). Pulmonary function test (PFT) was performed before and following the 6th day of operation. RESULTS: TNF-alpha, IL-6, IL-8 increased in both groups at T3, T4, T5 and T6 compared to control (p<0.05). TNF-alpha, IL-6, and IL-8 levels were lower in group A at T3, T4, T5 and T6 (p<0.05). Creatinin phosphokinase (CK) levels were lower in group A at T6 (p<0.05). CK-MB levels were lower in group A than in group C (p<0.05). Pulmonary function test (PFT) did not yield any differences between the groups. CONCLUSIONS: Preoperative allopurinol administration decreases the inflammation and myocardial injury according to biochemical markers of ischemia reperfusion injury. However, this biochemical success does not rebound to PFT (Tab. 5, Ref. 15).

The effects of intrathecal morphine on patient-controlled analgesia, morphine consumption, postoperative pain and satisfaction scores in patients undergoing gynaecological oncological surgery.

OBJECTIVE: Gynaecological oncological surgery (GOS) includes a wide variety of surgical procedures and postoperative pain is a major concern. This study compared the impact of intrathecal morphine (ITM) plus patient-controlled analgesia (PCA) with PCA alone on morphine consumption, pain relief and patient satisfaction after GOS. METHODS: Sixty women undergoing GOS under general anaesthesia were randomized to receive either 0.3 mg ITM or placebo. On arrival at the postanaesthesia care unit each patient received a morphine PCA pump. The three primary outcome measures were pain, patient satisfaction scores evaluated using a 100-mm visual analogue scale and cumulative PCA morphine consumption. RESULTS: No significant differences were observed in the demographic data. Cumulative PCA morphine consumption was significantly lower in the ITM group compared with the control group. Fatigue scores were lower in the ITM group compared with the control group but did not reach statistical significance. Pain, sedation and patient satisfaction scores, and the rate of side-effects were similar for the two groups. CONCLUSIONS: Administering ITM in GOS could improve postoperative analgesia and reduce morphine consumption without serious side-effects.

The role of immunonutrition in gynecologic oncologic surgery.

BACKGROUND: This study assesses the effect of immunonutrition on biochemical and hematological parameters, incidence of infection, postoperative complications, mortality rate and length of hospital stay. MATERIAL AND METHODS: A total of 50 patients operated on for gynecological malignancies were randomly assigned to two groups, each receiving two days preoperative and seven days postoperative enteral nutrition after intestinal movements started. The patients in group 1 were given 1000 kcal/d immun-enhancing enteral nutrition (IEN). The patients in group 2 received 1000 kcal/d standard enteral nutrition. The nutritional (albumin, prealbumin), immunologic (CRP, white blood cell (WBC) count, lymphocyte population) parameters, length of hospital stay (LOS) and clinical outcomes were examined. RESULTS: The two groups did not differ in terms of demographic data, nutritional status, surgical status, mortality rate (p > 0.05). WBC count, lymphocyte population, CRP levels were significantly higher in group 1 compared with group 2 in the postoperative period (p < 0.05). Pulmonary and urinary tract infection rates were similar in both groups (p > 0.05) but wound infection, and LOS rate were significantly lower in group 1 than group 2 (p < 0.05). CONCLUSION: Perioperative immunonutrition proved to be safe and useful in increasing the immunologic response. It may decrease postoperative complications and LOS in patients undergoing surgery for gynecological malignancy.

Protective role of zinc pretreatment in hepatotoxicity induced by halothane.

BACKGROUND AND OBJECTIVE: This study was designed to determine the protective effects of zinc on halothane induced hepatotoxicity. METHODS: Forty-five male Sprague-Dawley rats were divided into three groups. The halothane group received normal drinking water and diet; the zinc-halothane group received 227 mg L(-1) zinc sulphate in the drinking water and diet for 2 weeks; and the control group received normal diet and water. At the end of 2 weeks, rats were housed in an anaesthesia box and 1 MAC (minimum alveolar concentration)halothane was administered at 6 L min(-1) in room air for 2 h. This was repeated 48 h later. After the rats were sacrificed, we measured alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, gammaglutamyl transpeptidase, glutathione-S-transferase, serum electrolytes and bilirubin in samples. The degree of liver toxicity was assessed by light microscopic examination. RESULTS: We demonstrated a reduction of alanine aminotransferase, aspartate amino transferase, glutathione-S-transferase levels and a reduction in liver damage in the zinc-halothane group. CONCLUSION: The study concludes that zinc has the potential to alleviate the toxic effects of halothane in rat liver.

An investigation of non-depolarizing muscle relaxants on embryonic development in cultured rat embryos.

BACKGROUND AND OBJECTIVE: We have investigated the toxic and teratogenic effects of certain non-depolarizing muscle relaxants on embryonic development in cultured rat embryos. METHODS: Rat embryos of 9.5 days were explanted and cultured in vitro for 48 h in rat serum. Whole rat serum was used as a culture medium for the control group while different concentrations of atracurium, cis-atracurium, rocuronium and mivacurium were added to rat serum for the experimental groups. Dose-dependent effects of these agents on embryonic developmental parameters were compared using morphological and biochemical methods. Each embryo was evaluated for the presence of any malformations. RESULTS: When compared to the control embryos, the muscle relaxants significantly decreased all growth and developmental parameters dose dependently with an increase in overall dismorphology. Among these malformations, maxillary deformity was most frequently observed. These effects were observed in much lower doses with atracurium and cis-atracurium compared to those with rocuronium and mivacurium. CONCLUSIONS: Our results suggest that non-depolarizing muscle relaxants cause dose-dependent toxicity on rat embryos at concentrations much greater than those in clinical practice. Although, these agents seems to have a low potential for causing developmental toxicity during organogenesis, because of the lower toxic effects observed with rocuronium and mivacurium, these agents may be preferred when recurrent administrations are necessary for parturients.