Effect of Local Ketamine Subcutaneous Injection at the Incision Site in Reducing the Postoperative Pain Score after Transabdominal Hysterectomy.

Background: Pain control after operations is essential in decreasing the patient recovery period and potential morbidity. Prescribing opiates is very effective, but significant side effects accompany them. This study aims to examine the effect of local ketamine infiltration in decreasing pain intensity in patients undergoing transabdominal hysterectomy. Methods: In this double-blind, randomized, controlled clinical trial, a total of 92 patients undergoing transabdominal hysterectomy aged 30-60 years were selected and divided into two intervention and control groups randomly. For the intervention group, ketamine was injected subcutaneously into the incision site at a dose of 0.5 mg/kg after the operation. In the control group, 5 mg normal saline was used in the same method. Postoperative pain intensity was measured using the visual analog scale (VAS: 0-10). The pain score and dose of administered opioids were documented at 1, 2, 4, 6, 12, and 24 hours and compared between the two groups. Results: Postoperative pain intensity was significantly lower in the intervention group than in the control group, except for hour 24. The mean amounts of administered opioids were significantly lower in the intervention group at hours 6 and 12, as well as the total amount of used opioids, and no significant side effects were documented. Conclusion: Local ketamine subcutaneous injection in the incisional site is effective and is a safe procedure for reducing pain scores in patients who underwent a transabdominal hysterectomy.

Effects of nebulized hypertonic saline on inflammatory mediators in patients with severe COVID-19 pneumonia: A double-blinded randomized controlled trial.

INTRODUCTION: An exaggerated immune response is considered the most important aspect of COVID-19 pathogenesis. Hypertonic saline (HS) has shown promise in combating inflammation in several respiratory diseases. We investigated the effects of nebulized HS on clinical symptoms and inflammatory status in patients with severe novel coronavirus infection (COVID-19) pneumonia. MATERIALS AND METHODS: We randomly assigned 60 adults admitted to the intensive care unit (ICU) due to severe COVID-19 pneumonia to the experimental (received nebulized 5% saline) and control (received nebulized distilled water) groups. All interventions were applied 4 times daily for 5 days. The levels of tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), and other clinical factors from venous blood were evaluated before and after intervention application. Mortality rate, intubation rate, and durations of ICU and hospital stay were also compared between groups. RESULTS: The levels of TNF-α (MD: -21.35 [-32.29, -10.40], P = 0.000) and IL-6 (-9.94 [-18.86, -1.02], P = 0.003) were lower in the experimental group compared to the control group after applying the interventions. The levels of white blood cell count, PO2, and serum sodium were also statistically significant differences between groups. However, we did not observe significant differences in terms of hospitalization durations and mortality rates. CONCLUSION: Nebulization of HS in patients with severe COVID-19 pneumonia appears to be effective in reducing inflammation, but does not appear to affect intubation rates, mortality, hospitalization, or length of stay in ICU.

Gargle test for successful extubation in critically ill patients underwent head and neck surgeries: A new test.

Background: Improvement of predictive tools for recognition of airway edema is crucial for safe extubation and patient safety. This study aimed to evaluate the diagnostic accuracy of the Gargle test (GT) as a new test for assessing airway edema and predicting successful extubation in patients admitted to the intensive care unit (ICU). Method: In this prospective observational study, patients underwent head and neck surgeries and admitted to ICU included. All the patients were weaned based on the same protocol.Quantitative Cuff Leak Test (CLT) and qualitative CLTwere first applied followed by GT with normal saline 0.9%. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated. Results: One hundred and eighteen (male 67, female 51) participated in this study. The agreement between GT and CLT was low (Kappa: quantitative CLT 0.07, qualitative CLT 0.21). The GT compared to CLT had higher sensitivity (33.3% vs 16.6%), specificity (96.3% vs qualitative CLT 92.8%, quantitative CLT 79.4%), PPV (33.3% vs qualitative CLT 11.11%, quantitative CLT 4.0%), NPV (96.3% vs qualitative CLT 95.4%, quantitative CLT 94.6%), and accuracy (92.92% vs qualitative CLT 88.98%, quantitative CLT 76.27%. The cut-off value for GT was estimated 16.5% (sensitivity 74.1% and specificity 60%). Conclusion: The GT is a simple accurate test and can be used as a new test in the ICU for recognition of airway edema and prediction of safe extubation in patients with head and neck surgeries.

Mortality Predictive Value of APACHE II and SOFA Scores in COVID-19 Patients in the Intensive Care Unit.

Background: COVID-19 pandemic has become a global dilemma since December 2019. Are the standard scores, such as acute physiology and chronic health evaluation (APACHE II) and sequential organ failure assessment (SOFA) score, accurate for predicting the mortality rate of COVID-19 or the need for new scores? We aimed to evaluate the mortality predictive value of APACHE II and SOFA scores in critically ill COVID-19 patients. Methods: In a cohort study, we enrolled 204 confirmed COVID-19 patients admitted to the intensive care units at the Imam Khomeini hospital complex. APACHE II on the first day and daily SOFA scoring were performed. The primary outcome was the mortality rate in the nonsurvived and survived groups, and the secondary outcome was organ dysfunction. Two groups of survived and nonsurvived patients were compared by the chi-square test for categorical variables and an independent sample t-test for continuous variables. We used logistic regression models to estimate the mortality risk of high APACHE II and SOFA scores. Result: Among 204 severe COVID-19 patients, 114 patients (55.9%) expired and 169 patients (82.8%) had at least one comorbidity that 103 (60.9%) of them did not survive (P=0.002). Invasive mechanical ventilation and its duration were significantly different between survived and nonsurvived groups (P ≤ 0.001 and P=0.002, respectively). Mean APACHE II and mean SOFA scores were significantly higher in the nonsurvived than in the survived group (14.4 ± 5.7 vs. 9.5 ± 5.1, P ≤ 0.001, 7.3 ± 3.1 vs. 3.1 ± 1.1, P ≤ 0.001, respectively). The area under the curve was 89.5% for SOFA and 73% for the APACHE II score. Respiratory diseases and malignancy were risk factors for the mortality rate (P=0.004 and P=0.007, respectively) against diabetes and hypertension. Conclusion: The daily SOFA was a better mortality predictor than the APACHE II in critically ill COVID-19 patients. But they could not predict death with high accuracy. We need new scoring with consideration of the prognostic factors and daily evaluation of changes in clinical conditions.

Deciding When to Intubate a COVID-19 Patient.

Background: The SARS-CoV-2 pandemic is one of the most significant challenges for healthcare providers, particularly in the critical care setting. The timing of intubation in COVID-19 patients seems to be challenging. Therefore, we aimed to investigate how it may have a survival benefit, and we determined which clinical characteristics were associated with outcomes. Methods: This cross-sectional study was conducted in the Imam Khomeini Hospital Complex. We randomly selected patients admitted to intensive care units and, based on intubation status, categorized them into three subgroups (early, late, and not intubated). Early intubation is defined as intubation within 48 hours of ICU admission, and late intubation is defined as intubation after 48 hours of ICU admission. Results: Early-intubated patients were more likely to have dyspnea than late-intubated patients, and late-intubated patients had a higher mean heart rate than early-intubated patients. The neutrophil/lymphocyte ratio was significantly (P < 0.05) lower in not-intubated patients than in other patients. There was no difference in NLR between early- and late-intubated patients. Mean serum creatine phosphokinase and troponin I levels were higher in late-intubated patients than in early- and not-intubated patients. Early-intubated patients had a lower ROX index than late-intubated patients. Patients with higher scores of APACHE 2, respiratory rates, and neutrophil to lymphocyte ratio were more likely to be intubated. Increasing APACHE and SOFA scores were associated with decreased odds of survival. Conclusions: There were no statistically significant differences in total mortality between early- and late-intubated patients. APACHE 2 scores, NLR, RR, and history of ischemic heart disease are some of the appropriate predictors of intubation. Higher respiratory rates (tachypnea) can be an indicator of early intubation. The ROX index is one of the most sensitive and capable tools for predicting intubation. Intubation status is a potent predictor of in-hospital mortality.

The effect of supplementation with vitamins A, B, C, D, and E on disease severity and inflammatory responses in patients with COVID-19: a randomized clinical trial.

BACKGROUND AND OBJECTIVE: Because of the effect of vitamins on modulating the immune system function, we have evaluated the effect of supplementation with vitamins A, B, C, D, and E in ICU-admitted patients with COVID-19. METHODS: This study was a randomized and single-blinded clinical trial in which 60 subjects were randomly assigned to two groups. The intervention group (n=30) received vitamins, and the control group did not receive any vitamin or placebo. The intervention was included 25,000 IU daily of vitamins A, 600,000 IU once during the study of D, 300 IU twice daily of E, 500 mg four times daily of C, and one amp daily of B complex for 7 days. At baseline and after the 7-day intervention, the serum levels of inflammatory markers, vitamins, and the SOFA score were assessed. In addition, the mortality rate and duration of hospitalization were evaluated after the intervention (IRCT registration number: IRCT20200319046819N1/registration date: 2020-04-04, https://www.irct.ir/trial/46838 ). RESULTS: Significant changes were detected in serum levels of vitamins (p < 0.001 for all vitamins), ESR (p < 0.001), CRP (p = 0.001), IL6 (p = 0.003), TNF-a (p = 0.001), and SOFA score (p < 0.001) after intervention compared with the control group. The effect of vitamins on the mortality rate was not statistically significant (p=0.112). The prolonged hospitalization rate to more than 7 days was significantly lower in the intervention group than the control group (p=0.001). Regarding the effect size, there was a significant and inverse association between receiving the intervention and prolonged hospitalization (OR = 0.135, 95% CI 0.038-0.481; p=0.002); however, after adjusting for confounders, it was not significant (OR=0.402, 95% CI 0.086-1.883; p=0.247). CONCLUSION: Supplementation with vitamins A, B, C, D, and E could improve the inflammatory response and decrease the severity of disease in ICU-admitted patients with COVID-19.

The association between serum levels of micronutrients and the severity of disease in patients with COVID-19.

OBJECTIVES: This study aimed to compare the serum level of micronutrients with normal amounts, and assess their association with the severity of disease and inflammatory cytokines in patients with coronavirus disease 2019 (COVID-19). METHODS: The present cross-sectional study included 60 patients admitted to the intensive care unit with COVID-19. We recorded data on demographic characteristics, anthropometric information, and medical history. Serum levels of inflammatory markers (erythrocyte sedimentation rate, C-reactive protein, interferon-gamma, tumor necrosis factor-alpha, interleukin-6), vitamins (A, B9, B12, C, D, E), and minerals (magnesium, zinc, iron) were measured. A radiologist assessed the severity of lung involvement according to patient computed tomography scans. The severity of illness was evaluated with the Acute Physiologic Assessment and Chronic Health Evaluation (APACHE) score, oxygen saturation, and body temperature. Independent associations among the serum levels of micronutrients with the severity of COVID-19 were measured. RESULTS: Median patient age was 53.50 years (interquartile range, 12.75 years). Except for vitamin A and zinc, serum levels of other micronutrients were lower than the minimum normal. Patients with APACHE score ≥25 had a higher body mass index (P = 0.044), body temperature (P = 0.003), erythrocyte sedimentation rate (P = 0.008), C-reactive protein (P = 0.003), and lower oxygen saturation (P = 0.005), serum levels of vitamin D (P = < 0.001), and zinc (P = < 0.001) compared with patients with APACHE score <25. We found that lower serum levels of vitamin D, magnesium, and zinc were significantly and independently associated with higher APACHE scores (P = 0.001, 0.028, and < 0.001, respectively) and higher lung involvement (P = 0.002, 0.045, and < 0.001, respectively). CONCLUSIONS: Lower serum levels of vitamin D, zinc, and magnesium were involved in severe COVID-19.

Pathological Findings of Postmortem Biopsies From Lung, Heart, and Liver of 7 Deceased COVID-19 Patients.

Background. A novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been affecting almost all nations around the world. Most infected patients who have been admitted to intensive care units show SARS signs. In this study, we aimed to achieve a better understanding of pathological alterations that take place during the novel coronavirus infection in most presumed affected organs. Methods. We performed postmortem core needle biopsies from lung, heart, and liver on 7 deceased patients who had died of coronavirus disease 2019. Prepared tissue sections were observed by 2 expert pathologists. Results. Diffuse alveolar damage was the main pathologic finding in the lung tissue samples. Patients with hospitalization durations of more than 10 days showed evidence of organization. Multinucleated cells in alveolar spaces and alveolar walls, atypical enlarged cells, accumulation of macrophages in alveolar spaces, and congestion of vascular channels were the other histopathologic alteration of the lung. None of our heart biopsy samples met the criteria for myocarditis. Liver biopsies showed congestion, micro- and macro-vesicular changes, and minimal to mild portal inflammation, in the majority of cases. Conclusions. Similar to the previous coronavirus infection in 2003, the main pathologic finding in the lung was diffuse alveolar damage with a pattern of organization in prolonged cases. The SARS-CoV-2 infection does not cause myocarditis, and the ischemia of myocardium is the most probable justification of the observed pathologic changes in the heart. Liver tissue sections mostly showed nonspecific findings; however, ischemia of the liver can be identified in some cases.

Clinical Characteristics and Outcomes of 905 COVID-19 Patients Admitted to Imam Khomeini Hospital Complex in the Capital City of Tehran, Iran.

BACKGROUND: We studied the clinical characteristics and outcomes of 905 hospitalized coronavirus disease 2019 (COVID-19) patients admitted to Imam Khomeini Hospital Complex (IKHC), Tehran, Iran. METHODS: COVID-19 patients were recruited based on clinical symptoms and patterns of computed tomography (CT) imaging between February 20 and March 19. All patients were tested for the presence of COVID-19 RNA. The Poisson regression model estimated the incidence rate ratio (IRR) for different parameters. RESULTS: The average age (± standard deviation) was 56.9 (±15.7) years and 61.77% were male. The most common symptoms were fever (93.59%), dry cough (79.78%), and dyspnea (75.69%). Only 43.76% of patients were positive for the RT-PCR COVID-19 test. Prevalence of lymphopenia was 42.9% and more than 90% had elevated lactate dehydrogenase (LDH) or C-reactive protein (CRP). About 11% were severe cases, and 13.7% died in the hospital. The median length of stay (LOS) was 3 days. We found higher risks of mortality in patients who were older than 70 years (IRR = 11.77, 95% CI 3.63-38.18), underwent mechanical ventilation (IRR = 7.36, 95% CI 5.06-10.7), were admitted to the intensive care unit (ICU) (IRR = 5.47, 95% CI 4.00-8.38), tested positive on the COVID-19 test (IRR = 2.80, 95% CI 1.64-3.55), and reported a history of comorbidity (IRR = 1.76, 95% CI 1.07-2.89) compared to their corresponding reference groups. Hydroxychloroquine therapy was not associated with mortality in our study. CONCLUSION: Older age, experiencing a severe form of the disease, and having a comorbidity were the most important prognostic factors for COVID-19 infection. Larger studies are needed to perform further subgroup analyses and verify high-risk groups.

Impact of vitamins A, B, C, D, and E supplementation on improvement and mortality rate in ICU patients with coronavirus-19: a structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: This study will evaluate the main hypothesis that supplementation with vitamins A, B, C, D, and E significantly improves the severity and mortality rate in ICU patients with COVID-19. TRIAL DESIGN: This study is a randomized, single-blinded, two-arm (1:1 ratio) parallel group clinical trial. PARTICIPANTS: We are conducting this study in patients with COVID-19 admitted to intensive care units at the Imam Khomeini Hospital Complex in Tehran, Iran. The inclusion criteria are as follows: (1) aged between 20 and 60 years, (2) both male and female patients with COVID-19, (3) clinical or definitive diagnosis (using polymerase chain reaction (PCR) test), (4) patients have not participated in other clinical trials, and (5) no renal or hepatic abnormalities. The exclusion criteria are as follows: (1) patients with specific and rare viral diseases such as HIV and (2) patients who have been undergoing chemotherapy for the past month. INTERVENTION AND COMPARATOR: Duration of intervention: 7 days from randomization Intervention in the treatment group: Vitamin A 25,000 IU daily Vitamin D 600,000 IU once during study Vitamin E 300 IU twice daily Vitamin C is taken four times per day B vitamins are taken as a daily Soluvit [which included thiamine nitrate 3.1 mg, sodium riboflavin phosphate 4.9 mg (corresponding to vitamin B2 3.6 mg), nicotinamide 40 mg, pyridoxine hydrochloride 4.9 mg (corresponding to vitamin B6 4.0 mg), sodium pantothenate 16.5 mg (corresponding to pantothenic acid 15 mg), sodium ascorbate 113 mg (corresponding to vitamin C 100 mg), biotin 60 µg, folic acid 400 µg, and cyanocobalamin 5 µg] The control group will not receive any supplements or placebo. All supplements are made in Iran except for Soluvit (from Fresenius Kabi, New Zealand). MAIN OUTCOMES: 1. Weight, height, and BMI 2. Severity of pulmonary involvement according to CT scan 3. Respiratory support (invasive or non-invasive) 4. Percentage of oxygen saturation (SpO2 level) 5. Serum levels of WBC, CRP, ESR, IL6, IFN-G, and TNF-α 6. The patient's body temperature 7. The presence or absence of involvement of organs other than the lungs (e.g., heart, liver, kidneys) 8. Duration of hospitalization 9. Mortality rate RANDOMIZATION: At baseline, eligible patients were randomly assigned to a 1:1 ratio to one of two groups: intervention and control. Block randomization is used based on the gender of patients. BLINDING (MASKING): Patients are unaware of being placed in the intervention or control groups after signing consent. All treatment staff will be aware of which group each of the patients is in due to the specific conditions of the ICU and the absence of placebo for the control group. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): The researchers plan to include 60 patients in total, with 30 patients in each group. TRIAL STATUS: This is the first version of the protocol which started on April 2, 2020. Recruitment began April 2, 2020, and is expected to be complete by July 4, 2020. TRIAL REGISTRATION: The Iranian Registry of Clinical Trials IRCT20200319046819N1 . Registered on April 4, 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol (Fig. 1, Table 1).