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Objective:To investigate the efficacy of therapeutic plasma exchange with continuous renal replacement therapy in patients with early septic shock.Methods:A total of 55 patients with septic shock admitted to ICU of Mindong Hospital Affiliated to Fujian Medical University from December 2017 to December 2020 were retrospectively analyzed. The patients were divided into the therapeutic plasma exchange group ( n=29) and standard-therapy group ( n=26) according to whether plasma exchange combined with hemofiltration was used. Patients in both groups were treated according to the 2016 Surviving Sepsis Campaign guidelines. No hemofiltration or/and plasma exchange therapy was performed in the standard-therapy group. In the therapeutic plasma exchange group, hemofiltration was performed immediately after plasma exchange within 24 h. The inflammatory indexes, hemodynamic indexes, organ function scores and 28-day mortality were monitored before and 24 h after treatment. χ2 test was used for counting data, t-test was used for measurement data, and Kaplan-Meier curve was used to evaluate 28-day survival status. Results:(1) There were no differences in sex, age, underlying diseases, acute physiology and chronic health evaluationⅡ (APACHEⅡ) score and sequential organ failure assessment (SOFA) score before treatment between the two groups. (2) There were no significant differences in PCT, CRP and IL-6 between the two groups at enrollment. After treatment, PCT, CRP and IL-6 in the therapeutic plasma exchange group were significantly lower than those in the standard-therapy group [PCT (ng/mL): (50.07±14.54) vs. (57.93±13.42), P=0.043; CRP (mg/L): (85.71±46.05) vs. (115.10±44.42), P=0.042; IL-6 (pg/mL): (5 957.45±2 344.48) vs. (7 522.94±3 218.94), P=0.043], but there was no significant difference in WBC between the two groups. (3) There were no significant differences in norepinephrine dose, mean arterial pressure, heart rate, systemic vascular resistance index (SVRI), extravascular lung water index (EVLWI) and Lactate level between the two groups. After treatment, the norepinephrine dose, lactate level and EVLWI in the therapeutic plasma exchange group decreased significantly, while SVRI increased significantly {norepinephrine dose [μg/(kg·min): (0.76±0.39) vs. (0.54±0.39), P=0.044; lactate (μmmol/ L): (7.74±4.22) vs. (4.51±1.62), P<0.001; EVLWI (mL/kg): (10.04±2.77) vs. (8.23±2.23), P=0.008; SVRI (dyn·s/cm 2): (1 103.14±364.94) vs. (1 403.31±264.46), P=0.001}. Compared with the standard-therapy, the 24-h intravenous infusion volume was significantly decreased [(3 852.07±686.43) mL vs. (4 474.81±572.71) mL, P=0.001]. (4) There were no significant differences in APACHEⅡscore and SOFA score between the two groups at enrollment. After treatment, the APACHEⅡscore and SOFA score of the therapeutic plasma exchange group were significantly lower than those of the standard-therapy group [APACHEⅡscore: (14.07±4.30) vs. (19.23±5.44), P<0.001; SOFA score: (9.93±1.16) vs. (11.69±1.81), P<0.001)]. There were no significant differences in ICU mortality and 28-day mortality between the two groups ( P>0.05). Conclusions:Therapeutic plasma exchange with continuous renal replacement therapy can reduce the inflammatory response and improve hemodynamics in patients with septic shock. However, 24 h treatment did not improve the mortality of patients.
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BackgroundThe novel coronavirus (CoV) severe acute respiratory syndrome (SARS)-CoV-2 outbreak started at the end of 2019 in Wuhan, China, and spread over 100 countries. SARS-CoV-2 uses the membrane protein Angiotensin I converting enzyme 2(ACE2) as a cell entry receptor. Indeed, it was reported that the balance of Renin-Angiotensin System (RAS), regulated by both ACE and ACE2, was altered in COVID-19 patients. It is controversial, however, whether commonly used anti-hypertensive drugs Angiotensin I converting enzyme inhibitor (ACEI) and Angiotensin II receptor blocker (ARB) shall be continued in the confirmed COVID-19 patients. This study was designed to investigate any difference in disease severity between COVID-19 patients with hypertension comorbidity. The included COVID-19 patients used ACEI, ARB, calcium channel blockers (CCB), beta blockers (BB), or thiazide to treat preexisting hypertension prior to the hospital were compared to patients who did not take any of those drugs. MethodsIn this multicentre retrospective study, clinical data of 511 COVID-19 patients were analyzed. Patients were categorized into six sub-groups of hypertension comorbidity based on treatment using one of anti-hypertension drugs (ACEI, ARB, CCB, BB, thiazide), or none. A meta-analysis was performed to evaluate the use of ACEI and ARB associated with pneumonia using published studies. FindingsAmong the elderly (age>65) COVID-19 patients with hypertension comorbidity, the risk of COVID-19-S (severe disease) was significantly decreased in patients who took ARB drugs prior to hospitalization compared to patients who took no drugs (OR=0{middle dot}343, 95% CI 0{middle dot}128-0{middle dot}916, p=0{middle dot}025). The meta-analysis showed that ARB use has positive effects associated with morbidity and mortality of pneumonia. InterpretationElderly (age>65) COVID-19 patients with hypertension comorbidity who are taking ARB anti-hypertension drugs may be less likely to develop severe lung disease compared to patients who take no anti-hypertension drugs. FundingNational Natural Science Foundation of China, Chinese Academy of Medical Sciences Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed for articles published up to March 15, 2020 using keywords "2019-nCoV", "SARS-CoV-2", "novel coronavirus", and COVID-19 AND "ARB", and "angiotensin II receptor blocker" for papers published in both English and Chinese. We found three papers: one from our group, published in Science China Life Science that demonstrated an elevated Angiotensin II level in blood samples from COVID-19 patients; another a perspective article in Chinese recommending ACEI and ARBs as potential remedies for SARS-CoV-2 infections; the third a retrospective study in Chinese identifying no significant difference between ACEI/ARB associated with outcomes in 112 COVID-19 patients with CVD comorbidity. The International society of Hypertension stated on March 16th, 2020: "there are no clinical data in human to show that ACE-inhibitors or ARBs either improve or worsen susceptibility to COVID-19 infection nor do they affect the outcomes of those infected". Added value of this studyWe retrospectively reviewed different types of anti-hypertensive drugs taken by COVID-19 patients with hypertension comorbidity prior to entering the hospital. We discovered that ARB hypertensive drugs were associated with a decreased risk of severe disease in elderly (age>65) COVID-19 patients (OR=0{middle dot}343, 95% CI 0{middle dot}128-0{middle dot}916, p=0{middle dot}025), the first evidence of ARBs association to COVID-19 infections in human. We conducted a meta-analysis in the literature and found that ARB has positive effects associated with morbidity and mortality of pneumonia. Implications of all the available evidenceARB drugs are widely used in the population with hypertension. Treatments with ACEI and ARBs should be continuous according to medical guidelines. RCT trials of ARB associated with morbidity and mortality of SARS-CoV-2 infection are recommended in the future.
