Evaluation of characteristics and prognosis of COVID-19 patients requiring invasive mechanical ventilation during dominance of nonvariant, alpha, delta, and omicron variants in tertiary hospitals of Japan.

BACKGROUND: In November 2021, the B.1.1.529 (omicron) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was detected in South Africa and subsequently rapidly spread around the world. Despite the reduced severity of the omicron variants, many patients become severely ill after infection and undergo invasive mechanical ventilation, but there are few reports on their background and prognosis throughout all variant periods. This study aimed to evaluate risk factors affecting patients requiring invasive mechanical ventilation with each variant of COVID-19 pandemic in Japan from nonvariants to omicron variants. METHOD: This retrospective observational study was conducted at the Department of Emergency and Critical Care Medicine, Kansai Medical University Hospital and Kansai Medical University Medical Center, Osaka, Japan, from March 2020 to March 2023. Eligible patients were those who underwent invasive ventilation for COVID-19 pneumonia. We set the primary endpoint as in-hospital mortality. Multivariable logistic regression analysis adjusted for clinically important variables was performed to evaluate the clinical outcomes. RESULTS: We included 377 patients: 118 in the Nonvariant group, 154 in the Alpha group, 42 in the Delta group, and 63 patients in the Omicron group. Mortality rates for each group were 23.7% for the Nonvariant group, 12.3% for the Alpha group, 7.1% for the Delta group, and 30.5% for the Omicron group. Patient age was significantly associated with increased mortality (adjusted odds ratio [AOR]: 1.097; 95% confidence interval [CI]: 1.057-0.138, P < 0.001). Immunodeficiency (AOR: 3.388, 95% CI: 1.377-8.333, P = 0.008), initial SOFA score (AOR: 1.190, 95% CI: 1.056-1.341, P = 0.004), dialysis prior to COVID-19 (AOR: 3.695, 95% CI: 1.117-11.663, P = 0.026), and smoking history (AOR: 2.548, 95% CI: 1.153-5.628, P = 0.021) were significantly associated with increased mortality. Differences in variants were not significant factors associated with high mortality. CONCLUSION: We compared the background and prognosis of patients with COVID-19 pneumonia requiring invasive mechanical ventilation between SARS-CoV-2 variants. In these patients, differences in variants did not affect prognosis. Hospital mortality in critically ill COVID-19 patients was significantly higher in the older patients with bacterial coinfection, or patients with immunodeficiency, COPD, and chronic renal failure on dialysis.

Study of damage control strategy for non-traumatic diseases: a single-center observational study.

BACKGROUND: Damage control strategy (DCS) has been introduced not only for trauma but also for acute abdomen, but its indications and usefulness have not been clarified. We examined clinical characteristics of patients who underwent DCS and compared clinical characteristics and results with and without DCS in patients with septic shock. METHODS: We targeted a series of endogenous abdominal diseases in Kansai Medical University Hospital from April 2013 to March 2019. Clinical characteristics of 26 patients who underwent DCS were examined. Then, clinical characteristics and results were compared between the DCS group (n = 26) and non-DCS group (n = 31) in 57 patients with septic shock during the same period. RESULTS: All 26 patients who underwent DCS had septic shock, low mean arterial pressure (MAP) before the start of surgery, and required high-dose norepinephrine administration intraoperatively. Their discharge mortality rate was 12%. Among the patients with septic shock, the DCS group had a higher SOFA score (P = 0.008) and MAP was lower preoperatively, but it did not increase even with intraoperative administration of large amounts of fluid replacement and vasoconstrictor. There was no significant difference in 28-day mortality and discharge mortality between the two groups. CONCLUSIONS: DCS may be useful in patients with severe septic shock.

Lacosamide poisoning improved by hemodialysis.

Background: Lacosamide (LCM) is a third-generation antiepileptic drug that has been proven to be effective and safe, with few side-effects. Case Presentation: A woman aged in her 20s was transported to our hospital because of decreased consciousness. Many drugs, such as LCM (328 tablets) and perampanel hydrate (81 tablets), were found in her car. Her Glasgow Coma Scale score was 14. She was intubated and managed with mechanical ventilation, and she was treated with activated charcoal. Subsequently, hemodialysis (HD) was initiated due to the appearance of clonic convulsions. After 4 h of HD, no seizures were noted. The patient was weaned from the ventilator 18 h after admission and discharged on day 4. Her blood LCM level was 91.7 µg/mL on admission and 68.1 and 18.3 µg/ml before and after HD, respectively. Conclusion: Hemodialysis was carried out in this severe case of LCM poisoning and was found to be effective.

Evaluation of urinary extravasation after non-operative management of traumatic renal injury: a multi-center retrospective study.

PURPOSE: Urinary extravasation is one of the major complications after non-operative management of traumatic renal injury and may lead to urinary tract infection and sepsis. The purpose of this study was to evaluate these factors in patients with traumatic renal injury. METHODS: This was a multi-center, retrospective, observational study performed at three tertiary referral hospitals in Osaka prefecture. We included patients with traumatic renal injury transported to the centers between January 2008 and December 2018. We excluded patients who either died or underwent nephrectomy within 24 h after admission. We investigated the occurrence of urinary extravasation and the related factors after traumatic renal injury using multivariable logistic regression analysis. RESULTS: In total, 146 patients were eligible for analysis. Their median age was 44 years and 68.5% were male. Their median Injury Severity Score was 17. Renal injuries were graded as American Association for Surgery of Trauma (AAST) grade I in 33 (22.6%), II in 27 (18.5%), III in 38 (26.0%), IV in 28 (19.2%), and V in 20 (13.7%) patients. Urinary extravasation was diagnosed in 26 patients (17.8%) and was statistically significantly associated with AAST grades IV-V (adjusted odds ratio, 33.8 [95% confidence interval 7.12-160], p < 0.001). CONCLUSION: We observed urinary extravasation in 17.8% of patients with non-operative management of traumatic renal injury and the diagnosed was made in mostly within 7 days after admission. In this study, the patients with AAST grade IV-V injury were associated with having urinary extravasation.

Propofol suppresses ventricular arrhythmias: a case report of acute caffeine intoxication.

BACKGROUND: Caffeine is widely used as a stimulant drug throughout the world, and fatal arrhythmia is a known side-effect. We experienced a patient with caffeine intoxication causing fatal arrhythmias who was successfully treated with the infusion of propofol. CASE PRESENTATION: A 27-year-old woman was transferred to our hospital with nausea and poor general condition after intentional ingestion of 23.2 g of caffeine tablets. She was in cardiac arrest due to ventricular fibrillation just before hospital arrival. Advanced life support including defibrillation was started immediately, and we succeeded in resuscitating her 23 min later. Although she suffered from polymorphic ventricular premature beats and frequent transition to ventricular fibrillation, propofol administration converted her from a ventricular arrhythmia to sinus rhythm. CONCLUSION: We report this case focusing on the cardiovascular effects of propofol and the lipid sink phenomenon. As a result, propofol could have the potential to suppress ventricular arrhythmias.

Factors associated with bowel necrosis in patients with hepatic portal venous gas and pneumatosis intestinalis.

AIM: Historically, the presence of hepatic portal venous gas (HPVG) and pneumatosis intestinalis (PI) have been reported to be associated with bowel necrosis and fatal outcome. However, there are no criteria to judge whether bowel necrosis has occurred. We aimed to examine the factors associated with bowel necrosis in patients with HPVG and PI. METHODS: The study comprised 25 patients who were diagnosed as having HPVG and/or PI based on computed tomography (CT) findings in the Department of Emergency and Critical Care Medicine, Kansai Medical University Hospital (Osaka, Japan) between April 2013 and August 2017. We compared various factors, including clinical history, severity of present illness, laboratory data, and CT findings, and examined whether they were related to bowel necrosis. RESULTS: Both Sequential Organ Failure Assessment scores and total bilirubin levels were significantly higher in the necrosis group than those in the non-necrosis group (P = 0.03 and P = 0.02, respectively). The quantity of portal venous gas observed on computed tomography was associated with bowel necrosis in patients with HPVG. In contrast, the presence of air-type PI, defined as PI with emphysema covering the total circumference of the intestine in the absence of wall edema, and the presence of free air were significantly higher in the non-necrosis group (both P < 0.01). CONCLUSIONS: This study showed that the quantity of HPVG was associated with bowel necrosis, whereas the presence of free air or air-type PI was associated with non-necrosis of the bowel.

A strategy for improving the prognosis of non-occlusive mesenteric ischemia (NOMI): a single-center observational study.

AIM: The purpose of this study was to determine the prognostic factors of non-occlusive mesenteric ischemia (NOMI) and to examine treatment strategies that could improve its prognosis. METHODS: We retrospectively identified 30 patients who underwent emergency laparotomy for NOMI in Kansai Medical University Hospital (Hirakata, Japan) from April 2013 to December 2017. We examined prognostic factors related to discharge outcome and also examined the prognostic impact of open abdominal management and second look operation strategy (OSS) by dividing the patients into the non-OSS group and the OSS group. RESULTS: The primary end-point was a prognostic factor for outcome at discharge of the 30 patients. The outcome at discharge was compared between the survival group and the death group. Multivariate analysis was undertaken on two items from the univariate analysis that showed a significant difference (computed tomography findings of intestinal pneumatosis and acute disseminated intravascular coagulation [DIC] score). As a result, there was a significant difference in the factors of intestinal pneumatosis (odds ratio = 0.054; 95% confidence interval, 0.005-0.607; P = 0.018) and DIC score (odds ratio = 1.892; 95% confidence interval, 1.077-3.323; P = 0.027). The secondary end-point was the treatment outcome before and after the application of OSS. Operation time was significantly shorter and the amount of bleeding was also significantly less in the OSS group. CONCLUSION: Computed tomography findings of intestinal pneumatosis and the acute disseminated intravascular coagulation score were found to be prognostic factors for survival in patients with NOMI. Aggressive laparotomy to determine the definitive diagnosis is needed and OSS could be useful to improve patient prognosis for survival from NOMI.

Gastric emphysema with portal emphysema due to superior mesenteric artery syndrome developing septic shock: a case report.

BACKGROUND: Superior mesenteric artery syndrome (SMAS) is often associated with gastric dilatation but, very rarely, it can be associated with gastric emphysema. In addition, there are few reported cases accompanied by septic shock. CASE PRESENTATION: A 64-year-old man was transferred to our hospital with vomiting and abdominal distention. He went into shock and showed impaired consciousness. Blood biochemistry tests showed elevated levels of C-reactive protein. An abdominal computed tomography scan revealed a dilated stomach and proximal duodenum, and constriction of the third portion of the duodenum with gastric and portal emphysema. We thus diagnosed him with gastric and portal emphysema associated with SMAS that progressed to septic shock. We treated him conservatively by giving antibiotics and undertaking gastric drainage and feeding by way of the jejunum through a double elementary diet tube. CONCLUSION: This is the first report to describe a case of SMAS with gastric and portal emphysema that progressed to septic shock.

Study of the prognostic factor of the colon perforation case with the pan-peritonitis that needed emergency surgery: a single-center observational study.

AIM: We divided patients treated with emergency surgery for pan-peritonitis caused by colon perforation into the survival group and the death group based on outcome at postoperative day 30 and examined the prognostic factors for colon perforation. METHODS: The prognostic factors for colon perforation in 76 consecutive patients who underwent emergency surgery at Kansai Medical University Hospital (Hirakata, Japan) from April 2011 to March 2017 were investigated based on outcome at postoperative day 30. RESULTS: The average age of the 76 patients (41 men/35 women) was 73 years, and the causative disease of colon perforation was malignant/benign in 18/58 cases, with ileocecal perforation site in 8 cases, ascending colon in 6, transverse colon in 2, descending colon in 4, sigmoid colon in 49, and rectum in 7. All patients received laparotomy with irrigation drainage, and 9 patients (11.8%) were dead at 30 days. Upon comparing the 67 survivors with the 9 dead patients, we recognized a significant difference on preoperative spread of ascites on computed tomography (CT) (P = 0.002) in univariate analysis and on acute disseminated intravascular coagulation (DIC) score (odds ratio 2.289; 95% confidence interval, 1.188-4.410; P = 0.013) in multivariate analysis. CONCLUSION: In our hospital, the preoperative acute DIC score was found to be a prognostic factor for colon perforation accompanied by pan-peritonitis. Appropriate evaluation of the spread of ascites on the preoperative CT might also help predict patient prognosis.

Takotsubo cardiomyopathy in the intensive care unit.

AIMS: An angiographic examination is necessary for the diagnosis of takotsubo cardiomyopathy (TTC). However, in the intensive care unit (ICU), intensivists often see patients in whom TTC cannot be diagnosed because they cannot undertake angiography due to the patient's poor general condition. We defined such cases as clinical TTC (cTTC) and investigated the incidence and background of cTTC in the ICU at Kansai Medical University Hospital (Osaka, Japan). METHODS: The study involved 5,084 patients who were admitted to the ICU of Kansai Medical University Hospital between January 2013 and December 2017. We retrospectively investigated the frequency and background of TTC and cTTC. RESULTS: Of the 5,084 patients, 5 (0.09%) patients admitted to the ICU were diagnosed as having TTC and 19 patients (0.37%) were diagnosed as having cTTC. The most common primary disease among the evaluated patients was sepsis (n = 10) followed by subarachnoid hemorrhage (SAH) (n = 5). Ten of the 335 patients with sepsis (3.0%) were admitted to the ICU with complications due to cTTC. Their blood pressure and heart rate on admission tended to be high, and their Sequential Organ Failure Assessment scores tended to be low. Five of the 172 patients with SAH (2.9%) were admitted to the ICU with complications due to cTTC. These patients were often classified as grade 5 on the Hunt and Hess scale. CONCLUSION: Our study suggests that patients with sepsis or SAH are complicated with cTTC in the ICU. In addition, there might be no correlation between the severity of sepsis and the development of TTC.

Ventricular septal perforation after blunt chest trauma due to blows from a fist.

Case: A 40-year-old man received fist blows to his chest and abdomen. He presented with external jugular vein distention and facial congestion. Chest X-ray showed bilateral pulmonary congestion. A Levine V/VI holosystolic murmur was audible. Echocardiography showed left-to-right shunt flow across the perimembranous region of the ventricular septum. The diameter of the hole was approximately 13 mm. We diagnosed ventricular septal perforation, started an infusion, and administered vasopressors. However, circulatory dynamics could not be maintained. The ventricular septal perforation was repaired directly with mattress sutures through the right ventricle. A small residual ventricular septal perforation was detected, which was repaired with a patch sutured through the left ventricle. Outcome: The patient was discharged without cardiovascular complications 43 days after admission. Conclusion: Ventricular septal perforation following blunt chest trauma is a rare form of cardiac trauma. It is important to consider the timing of the operation and the best method to ensure cardiac repair.

Vasodilating prostaglandin E1 does not reproduce interleukin-1ß-induced oxygen metabolism abnormalities in rabbits.

Background: We have reported that administration of recombinant human interleukin (IL)-1ß induced circulatory shock in rabbits by causing overproduction of vasodilating prostaglandin(s) and simultaneously impaired oxygen metabolism by causing an abnormal dependence of oxygen consumption (VO2) on oxygen delivery (DO2). The present study was carried out to compare the effect of administration of exogenous PGE1 with that of IL-1ß on oxygen metabolism. Methods: Sixteen rabbits were assigned to one of three groups and given a single injection of 10 µg/kg IL-1ß (IL-1ß group, n = 5), continuous infusion of 1 µg/kg/min PGE1 (PGE1 group, n = 6), or saline (control group, n = 5). All rabbits were subjected to stepwise cardiac tamponade to decrease DO2 by inflating a balloon placed into the pericardial sac. The VO2/DO2 relation was analyzed by the dual-line method. Results: Both IL-1ß and PGE1 decreased the baseline value of mean arterial pressure by approximately 25% without inducing significant alteration of the cardiac index. With respect to the VO2/DO2 relation, the slope of the supply-independent line was significantly increased in the IL-1ß group (y = 0.13x + 6.4), but not in the PGE1 group (y = 0.01x + 10.0) compared to that in the control group (y = 0.05x + 8.7). Conclusion: These results indicate that simple vasodilation and hypotension induced by administration of PGE1 are insufficient to account for the abnormal oxygen metabolism induced by IL-1ß.

Delayed formation of splenic pseudoaneurysm following nonoperative management in blunt splenic injury: multi-institutional study in Osaka, Japan.

BACKGROUND: Delayed rupture is well-known as a severe complication after splenic injury treated with nonoperative management (NOM). The incidence and timing of splenic pseudoaneurysm (SPA) formation, which is a cause of delayed rupture following splenic injury, have not been thoroughly investigated, and the timing of follow-up computed tomography (CT) is controversial. The objective of this study was to clarify the incidence and timing of both the delayed formation and spontaneous resolution of SPA following splenic injuries treated with NOM in several trauma centers in Japan. METHODS: This was a retrospective review of all patients with documented blunt splenic injury who were treated with NOM from 2003 through 2010 in five trauma and critical care centers. RESULTS: The present study consisted of 104 patients, including 16 patients (15.4%) with delayed formation of SPA (7 patients with Grade II and 9 with Grade III) during their clinical course. SPA was diagnosed with enhanced CT at a mean (SD) of 4.6 (2.1) hospital days (range, 1-8 days) after admission. Delayed formation of SPA was found in 30.4% of Grade II injuries and in 18.4% of Grade III injuries. Eight patients with delayed formation of SPA were observed without transcatheter arterial embolization during their entire stay. These SPAs were spontaneously occluded on follow-up enhanced CT or angiography. Spontaneous occlusion of SPA was confirmed at 5.2 (2.6) hospital days (range, 2-10 days) after diagnosis of delayed SPA. CONCLUSION: Delayed formation of SPAs was recognized with enhanced helical CT in 15% of all patients during hospital Days 1 to 8. About one half of the SPAs had occluded spontaneously without therapeutic intervention. Our results suggested that follow-up enhanced CT performed approximately 1 week after splenic injury may be useful to detect delayed SPA formation. LEVEL OF EVIDENCE: Epidemiologic study, level III.

Electrical vagus nerve stimulation attenuates systemic inflammation and improves survival in a rat heatstroke model.

This study was performed to gain insights into novel therapeutic approaches for the treatment of heatstroke. The central nervous system regulates peripheral immune responses via the vagus nerve, the primary neural component of the cholinergic anti-inflammatory pathway. Electrical vagus nerve stimulation (VNS) reportedly suppresses pro-inflammatory cytokine release in several models of inflammatory disease. Here, we evaluated whether electrical VNS attenuates severe heatstroke, which induces a systemic inflammatory response. Anesthetized rats were subjected to heat stress (41.5°C for 30 minutes) with/without electrical VNS. In the VNS-treated group, the cervical vagus nerve was stimulated with constant voltage (10 V, 2 ms, 5 Hz) for 20 minutes immediately after completion of heat stress. Sham-operated animals underwent the same procedure without stimulation under a normothermic condition. Seven-day mortality improved significantly in the VNS-treated group versus control group. Electrical VNS significantly suppressed induction of pro-inflammatory cytokines such as tumor necrosis factor-α and interleukin-6 in the serum 6 hours after heat stress. Simultaneously, the increase of soluble thrombomodulin and E-selectin following heat stress was also suppressed by VNS treatment, suggesting its protective effect on endothelium. Immunohistochemical analysis using tissue preparations obtained 6 hours after heat stress revealed that VNS treatment attenuated infiltration of inflammatory (CD11b-positive) cells in lung and spleen. Interestingly, most cells with increased CD11b positivity in response to heat stress did not express α7 nicotinic acetylcholine receptor in the spleen. These data indicate that electrical VNS modulated cholinergic anti-inflammatory pathway abnormalities induced by heat stress, and this protective effect was associated with improved mortality. These findings may provide a novel therapeutic strategy to combat severe heatstroke in the critical care setting.

Systemic involvement of high-mobility group box 1 protein and therapeutic effect of anti-high-mobility group box 1 protein antibody in a rat model of crush injury.

Patients with crush injury often present systemic inflammatory response syndrome and fall into multiple organ failure. The mechanism by which the local tissue damage induces distant organ failure is still unclear. We focused on high-mobility group box 1 protein (HMGB1) as one of the damage-associated molecular pattern molecules that cause systemic inflammation in crush injury. We investigated involvement of HMGB1 and the effects of treatment with anti-HMGB1 antibody in a rat model of crush injury. Both hindlimbs of rats were compressed for 6 h and then released. In the crush injury group, the level of serum HMGB1 peaked at 3 h after releasing compression, followed by the increasing in the serum levels of interleukin 6 and tumor necrosis factor α. Hematoxylin-eosin staining showed substantial damage in the lung 24 h after the crush injury, with upregulation of the expression of receptor for advanced glycation end products, as revealed by immunohistochemical analysis. Intravenous administration of anti-HMGB1 antibody improved survival (n = 20 each group) and significantly suppressed serum levels of HMGB1, interleukin 6, and tumor necrosis factor α compared with the untreated crush injury group (n = 6-9 each group). Histological findings of lung damage were ameliorated, and the expression of receptor for advanced glycation end products was hampered by the treatment. These results indicate that HMGB1 is released in response to damage immediately after crush injury and acts as a proinflammatory mediator. Administration of anti-HMGB1 antibody reduced inflammatory reactions and improved survival by blocking extracellular HMGB1. Thus, HMGB1 appears to be a therapeutic target, and anti-HMGB1 antibody may become a promising novel therapy against crush injury to prevent the progression to multiple organ failure.