Comprehensive analysis of immune responses in CLL patients after heterologous COVID-19 vaccination

Patients with chronic lymphocytic leukemia (CLL) treated with B-cell pathway inhibitors and anti-CD20 antibodies exhibit low humoral response rate (RR) following SARS-CoV-2 vaccination. To investigate the relationship between the initial transcriptional response to vaccination with ensuing B and T cell immune responses, we performed a comprehensive immune transcriptome analysis flanked by antibody and T cell assays in peripheral blood prospectively collected from 15 CLL/SLL patients vaccinated with heterologous BNT162b2/ChAdOx1 with follow up at a single institution. The two-dose antibody RR was 40% increasing to 53% after booster. Patients on BTKi, venetoclax {+/-} anti-CD20 antibody within 12 months of vaccination responded less well than those under BTKi alone. The two-dose T cell RR was 80% increasing to 93% after booster. Transcriptome studies revealed that seven patients showed interferon-mediated signaling activation within 2 days and one at 7 days after vaccination. Increasing counts of COVID-19 specific IGHV genes correlated with B-cell reconstitution and improved humoral RR. T cell responses in CLL patients appeared after vaccination regardless of treatment status. A higher humoral RR was associated with BTKi treatment and B-cell reconstitution. Boosting was particularly effective when intrinsic immune status was improved by CLL-treatment.

Genetic immune response and antibody repertoire of heterologous ChAdOx1-BNT162b2 vaccination in a Korean cohort

Heterologous ChAdOx1-BNT162b2 vaccination induces a stronger immune response than two doses of BNT162b2 or ChAdOx1. Yet, the molecular transcriptome, the germline allelic variants of immunoglobulin loci and anti-Omicron antibody levels induced by the heterologous vaccination have not been formally investigated. Moreover, there is a paucity of COVID vaccine studies including diverse genetic populations. Here, we show a robust molecular immune transcriptome and antibody repertoire in 51 office workers from the Republic of Korea after a heterologous ChAdOx1-BNT162b2 vaccination or a homologous ChAdOx1-ChAdOx1 vaccination. Anti-spike-specific IgG antibody levels in the heterologous group increased from 14,000 U/ml to 142,000 AU/ml within eight days after the BNT162b2 vaccination. In contrast, antibody levels in the homologous group increased two-fold after the second ChAdOx1 dose. Antibody titers against the Omicron spike protein as compared to the ancestral strain were reduced to a lesser extent in the heterologous group. RNA-seq conducted on immune cells demonstrated a stronger activation of interferon-induced genetic programs in the heterologous cohort. An increase of specific IGHV clonal transcripts encoding neutralizing antibodies was preferentially detected in the heterologous cohort. Enrichment of B cell and CD4+ T cell responses were observed following both heterologous and homologous vaccination using scRNA-seq, but clonally expanded memory B cells were relatively stronger in the ChAdOx1-BNT162b2 cohort. In summary, a heterologous vaccination with ChAdOx1 followed by BNT162b2 provides an innate and adaptive immune response exceeding that seen in homologous ChAdOx1 vaccinations but equivalent to that seen in homologous BNT162b2 vaccination.

Effect of corticosteroid therapy in the early phase of acute respiratory distress syndrome: a propensitymatched cohort study

Background/Aims@#It is unclear whether corticosteroid use in patients with acute respiratory distress syndrome (ARDS) improves survival. This study aimed to investigate whether the administration of corticosteroids to patients in the early phase of moderate to severe ARDS is associated with improved outcomes. @*Methods@#We analyzed the data of patients who received corticosteroids within 7 days of the onset of ARDS between June 2006 and December 2015 at a single tertiary teaching hospital. A total of 565 patients admitted with moderate to severe ARDS were eligible. The outcomes of patients treated with methylprednisolone 40 to 180 mg/day or equivalent (n = 404) were compared to those who did not receive steroids (n = 161). The primary and secondary outcomes were 28- and 90-day mortality rates, respectively. Propensity scores were used to adjust for baseline covariates. @*Results@#The overall mortality at 28 days was not significantly different between the corticosteroid-treated and control groups (43.8% vs. 41%, p = 0.541). At 90 days, the overall mortality rate was higher in the corticosteroid-treated group than in the control group (59.2% vs. 48.4%, p = 0.021). However, on propensity score matching, corticosteroid therapy was not associated with a higher 28-day mortality rate (odds ratio, 1.031; 95% confidence interval, 0.657 to 1.618; p = 0.895) and 90 days (odds ratio, 1.435; 95% confidence interval, 0.877 to 2.348; p = 0.151). @*Conclusions@#Corticosteroid therapy was not associated with 28- or 90-day mortality in the early phase of moderate to severe ARDS on propensity score matching analysis.

Comparison of rivaroxaban and dalteparin for the long-term treatment of venous thromboembolism in patients with gynecologic cancers / 부인종양

Comparison of rivaroxaban and dalteparin for the long-term treatment of venous thromboembolism in patients with gynecologic cancers / 부인종양

Objectives@#Two randomized, controlled studies comparing outcomes in patients treated with direct oral anticoagulants or low-molecular weight heparin for cancer-associated venous thromboembolism (VTE) have previously been performed. However, gynecologic cancers accounted for approximately 10% of the study populations. We compared the outcomes of patients with primary gynecological cancers who were treated for cancer-associated VTE with either rivaroxaban or dalteparin. @*Methods@#The 162 eligible patients with gynecologic cancers who were treated with either dalteparin (n=60) or rivaroxaban (n=102) were reviewed. The primary outcome was a composite event, which included recurrence or clinically relevant bleeding events during the therapeutic period. Secondary outcomes were recurrence, clinically relevant bleeding events, and mortality. @*Results@#During the therapeutic period, there were no significant differences between the groups in the proportion of composite events, recurrence, or clinically relevant bleeding. Multivariate analysis using the Cox proportional hazards model also showed no significant difference in the number of composite events and clinically relevant bleeding between the groups. In the rivaroxaban group, 44.0% of patients experienced gastrointestinal bleeding and 24.0% experienced urinary tract bleeding. In the dalteparin group, bleeding was most common in the urinary tract (44.4%) and at the injection site (22.2%). @*Conclusion@#In this study, although there were no significant differences in effectiveness or safety between the rivaroxaban and dalteparin groups, rivaroxaban use was associated with a higher rate of clinically relevant bleeding than dalteparin. Therefore, caution should be taken when prescribing rivaroxaban for gynecologic cancer-associated VTE and bleeding events should be carefully monitored.

Derivation and validation of modified early warning score plus SpO2/FiO2 score for predicting acute deterioration of patients with hematological malignancies

Background/Aims@#Scoring systems play an important role in predicting intensive care unit (ICU) admission or estimating the risk of death in critically ill patients with hematological malignancies. We evaluated the modified early warning score (MEWS) for predicting ICU admissions and in-hospital mortality among at-risk patients with hematological malignancies and developed an optimized MEWS. @*Methods@#We retrospectively analyzed derivation cohort patients with hematological malignancies who were managed by a medical emergency team (MET) in the general ward and prospectively validated the data. We compared the traditional MEWS with the MEWS plus SpO2/FiO2 (MEWS_SF) score, which were calculated at the time of MET contact. @*Results@#In the derivation cohort, the areas under the receiver-operating characteristic (AUROC) curves were 0.81 for the MEWS (95% confidence interval [CI], 0.76 to 0.87) and 0.87 for the MEWS_SF score (95% CI, 0.87 to 0.92) for predicting ICU admission. The AUROC curves were 0.70 for the MEWS (95% CI, 0.63 to 0.77) and 0.76 for the MEWS_SF score (95% CI, 0.70 to 0.83) for predicting in-hospital mortality. In the validation cohort, the AUROC curves were 0.71 for the MEWS (95% CI, 0.66 to 0.77) and 0.83 for the MEWS_SF score (95% CI, 0.78 to 0.87) for predicting ICU admission. The AUROC curves were 0.64 for the MEWS (95% CI, 0.57 to 0.70) and 0.74 for the MEWS_SF score (95% CI, 0.69 to 0.80) for predicting in-hospital mortality. @*Conclusions@#Compared to the traditional MEWS, the MEWS_SF score may be a useful tool that can be used in the general ward to identify deteriorating patients with hematological malignancies.

The quick sepsis-related organ failure score has limited value for predicting adverse outcomes in sepsis patients with liver cirrhosis

Background/Aims@#The quick Sepsis-related Organ Failure Assessment (qSOFA) is a newly developed risk stratification tool, which has been presented along with a new sepsis definition, to classify infected patients outside of the intensive care unit (ICU). We evaluated the clinical usefulness of qSOFA for predicting adverse outcomes in sepsis patients with liver cirrhosis. @*Methods@#We performed a retrospective cohort study to assess the utility of qSOFA in sepsis patients with liver cirrhosis for whom medical emergency teams (METs) were activated in general wards at an academic tertiary care hospital between March 2008 and December 2015. qSOFA, Systemic inflammatory response syndrome (SIRS), modified early warning score (MEWS), and sequential (sepsis- related) organ failure assessment (SOFA) scores were calculated according to data at MET activation. @*Results@#Of 188 patients, 69 (36.7%) had a qSOFA score of 0 or 1 point and 119 (63.3%) had ≥ 2 points. The areas under the receiver operating characteristic curve (AUROC) for ICU transfer on the SOFA (AUROC, 0.691; 95% confidence interval [CI], 0.615 to 0.767) or MEWS (AUROC, 0.663; 95% CI, 0.586 to 0.739) were significantly higher compared to those for qSOFA (AUROC, 0.589; 95% CI, 0.507 to 0.671) or SIRS (AUROC, 0.533; 95% CI, 0.451 to 0.616). @*Conclusions@#Our findings suggest that qSOFA score may have limited utility in predicting adverse outcomes in sepsis patients with liver cirrhosis at MET activation. Either MEWS or another screening tool is needed for detecting early sepsis in these patients.

Iatrogenic Opioid Withdrawal Syndrome in Critically Ill Patients: a Retrospective Cohort Study

Background@#Opioid withdrawal syndrome (OWS) may occur following the reduction or discontinuation of opioid analgesics. In critically ill pediatric patients, OWS is a common and clinically significant condition. However, OWS in adult patients has not been assessed in detail. Therefore, we aimed to investigate the incidence, risk factors, and clinical features of OWS in mechanically ventilated patients treated in an adult intensive care unit (ICU). @*Methods@#This study was a retrospective evaluation of data from patients treated in the medical ICU for > 3 days and who received only one type of opioid analgesic. OWS was assessed over a 24 hours period from discontinuation or reduction (by > 50%) of continuous opioid infusion. OWS was defined as the presence of ≥ 3 central nervous system or autonomic nervous system symptoms. @*Results@#In 126 patients treated with remifentanil (n = 58), fentanyl (n = 47), or morphine (n = 21), OWS was seen in 31.0%, 36.2%, and 9.5% of patients, respectively (P = 0.078). The most common symptom was a change in respiratory rate (remifentanil, 94.4%; fentanyl, 76.5%; morphine, 100%). Multivariate Cox-proportional hazards model showed that OWS was negatively associated with morphine treatment (hazard ratio [HR], 0.17; 95% confidence interval [CI], 0.037–0.743) and duration of opioid infusion (HR, 0.566; 95% CI, 0.451–0.712). @*Conclusion@#OWS is not uncommon in mechanically ventilated adult patients who received continuous infusion of opioids for > 3 days. The use of morphine may be associated with a decreased risk of OWS.

Safety of antimicrobial de-escalation for culture-negative severe pneumonia.

PURPOSE: This study investigated the outcomes of antimicrobial de-escalation (ADE) based on mortality and the incidence of multi-drug resistant (MDR) pathogen occurrence in patients with culture-negative pneumonia presenting with sepsis and septic shock. MATERIALS AND METHODS: We retrospectively analyzed patients diagnosed with severe pneumonia requiring intensive care unit (ICU) admission and possessing negative microbiological culture results at a tertiary referral hospital in South Korea from March 2008 to July 2018. RESULTS: We identified 107 patients with culture-negative pneumonia. The Acute Physiologic and Chronic Health Evaluation (APACHE) II and Sepsis-related Organ Failure Assessment (SOFA) mean scores were 20.3 ±â€¯8.6 and 9.6 ±â€¯3.3, respectively. Among the patients, 40 (37.4%) underwent ADE. The APACHE II, SOFA, and follow-up SOFA scores did not differ significantly between the groups, and no differences were found in ICU mortality and MDR pathogen occurrence (27.5% vs 41.8%, P = .137 and 15.0% vs 16.9% P = .794, respectively). CONCLUSIONS: We observed similar ICU mortality and MDR pathogen occurrence in patients with culture-negative pneumonia presenting with sepsis/shock regardless of whether they received ADE. Additionally, ADE lowered the antimicrobial burden.

Erratum: Effect of vitamin D deficiency in Korean patients with acute respiratory distress syndrome

There is a spelling mistake of an author's name, and the authors want to change to Min Gee Lee from Min Gi Lee.

The effect of an improvement of experience and training in extracorporeal membrane oxygenation management on clinical outcomes

BACKGROUND/AIMS@#The use of extracorporeal membrane oxygenation (ECMO) is spreading rapidly, with successful procedures reported in the ECMO for Severe Adult Respiratory failure (CESAR) trial and treatment of the H1N1 pandemic. However, ECMO is associated with a high mortality rate. This study aimed to show that increased experience and improved teamwork through education may reduce the mortality rate associated with ECMO.@*METHODS@#A retrospective study was performed. Data were collected from January 1, 2009, to December 31, 2011. The data were divided into two periods: 2009/2010 (period 1) and 2011 (period 2). The protocol and training program were applied during period 2.@*RESULTS@#Seventy-six patients were included. The most common disease requiring ECMO support was pneumonia (43.4%). ECMO was applied within 7 days in 76.3% of patients. The primary outcomes, such as Intensive Care Unit (ICU) and hospital mortality rates, were higher during period 1 (91.3%) than period 2 (66.7%, p = 0.013). A multivariate analysis revealed that ECMO weaning failure was the only factor associated with ICU and hospital mortality (ICU mortality: hazard ratio [HR], 11.349; 95% confidence interval [CI], 1.281 to 100.505; p = 0.029; hospital mortality: HR, 17.976; 95% CI, 2.263 to 142.777; p = 0.006).@*CONCLUSIONS@#The mortality rate associated with the ECMO procedure decreased following the ECMO training program. However, applying the training program to ECMO management is not an independent factor for the mortality rate. Further studies should be performed to help reduce the mortality rate associated with ECMO.

Effect of vitamin D deficiency in Korean patients with acute respiratory distress syndrome

BACKGROUND/AIMS: Vitamin D modulates innate and adaptive immune responses, and vitamin D deficiency is associated with increased mortality in hospitalized patients with pneumonia. We evaluated the prevalence of vitamin D deficiency in Korean patients with acute respiratory distress syndrome (ARDS) and its effect on the clinical outcomes of ARDS. METHODS: We retrospectively analyzed the data of 108 patients who had a measured serum level of 25-hydroxy vitamin D3 (25(OH)D3) at the time of diagnosis with ARDS. The clinical outcomes were evaluated based on 25(OH)D3 levels of 20 ng/mL and stratified by quartiles of 25(OH)D3 levels. RESULTS: The mean age of patients was 59.4 years old; 77 (71.3%) were male. Vitamin D deficiency was found in 103 patients (95.4%). The mean 25(OH)D3 level was 8.3 ± 7.0 ng/mL. Neither in-hospital mortality (40.0% vs. 68.0%) nor 6-month mortality (40.0% vs. 71.8%) significantly differed between groups. There were no significant differences in 25(OH)D3 level between survivors (8.1 ± 7.6 ng/mL) and non-survivors (8.5 ± 6.8 ng/mL, p = 0.765). There were no trends toward a difference in mortality among quartiles of 25(OH)D3 levels. However, 25(OH)D3 levels were inversely related with length of hospital stay and intensive care unit stay among in-hospital survivors. CONCLUSIONS: Vitamin D deficiency was prevalent in Korean patients with ARDS. However, levels of vitamin D were not associated with mortality. A large, prospective study is needed to evaluate the effects of vitamin D deficiency on clinical outcomes of ARDS.

Serial Changes in Mannose-Binding Lectin in Patients with Sepsis / 결핵및호흡기질환

BACKGROUND: Mannose-binding lectin (MBL) deficiency leads to increased susceptibility to infection. We investigated whether serial changes in MBL levels are associated with the prognosis of patients diagnosed with septic shock, and correlated with cytokine levels. METHODS: We enrolled 131 patients with septic shock in the study. We analyzed the serum samples for MBL and cytokine levels at baseline and 7 days later. Samples on day 7 were available in 73 patients. RESULTS: We divided the patients with septic shock into four groups according to serum MBL levels ( < 1.3 µg/mL or ≥1.3 µg/mL) on days 1 and 7. Patients with low MBL levels on day 1 and high MBL levels on day 7 showed a favorable prognosis for 28-day survival (odds ratio, 1.96, 95% confidence interval, 1.10–2.87; p=0.087). The high MBL group on day 7 showed a significant decrease in monocyte chemoattractant protein 1, interleukin (IL)-1β, IL-6, IL-8, interferon-γ, and granulocyte macrophage colony-stimulating factor levels compared with the low MBL group on day 7. CONCLUSION: The increase in MBL levels of patients with septic shock may suggest a favorable prognosis and attenuate pro-inflammatory and anti-inflammatory responses.

Ceftizoxime-induced immune hemolytic anemia associated with multi-organ failure / 영남의대학술지

Drug-induced immune hemolytic anemia (DIIHA) is a rare side effect of drugs. DIIHA may cause a systemic inflammatory response that results in acute multi-organ failure and death. Ceftizoxime belongs to the class of third generation cephalosporins, which are the most common drugs associated with DIIHA. Herein, we present a case of a 66-year-old man who developed fatal DIIHA after receiving a second dose of ceftizoxime. He was admitted to receive photodynamic therapy. He had a history of a single parenteral dose of ceftizoxime 3 months prior to admission. On the day of the procedure — shortly after the infusion of ceftizoxime — the patient's mental status was altered. The blood test results revealed hemolysis. Oliguric acute kidney injury developed, and continuous renal replacement therapy had to be applied. On the suspicion of DIIHA, the patient underwent plasmapheresis. Diagnosis was confirmed by a detection of drug-dependent antibody with immune complex formation. Although his hemolysis improved, his liver failure did not improve. He was eventually discharged to palliative care, and subsequently died.

Ceftizoxime-induced immune hemolytic anemia associated with multi-organ failure / 영남의대학술지

Drug-induced immune hemolytic anemia (DIIHA) is a rare side effect of drugs. DIIHA may cause a systemic inflammatory response that results in acute multi-organ failure and death. Ceftizoxime belongs to the class of third generation cephalosporins, which are the most common drugs associated with DIIHA. Herein, we present a case of a 66-year-old man who developed fatal DIIHA after receiving a second dose of ceftizoxime. He was admitted to receive photodynamic therapy. He had a history of a single parenteral dose of ceftizoxime 3 months prior to admission. On the day of the procedure — shortly after the infusion of ceftizoxime — the patient's mental status was altered. The blood test results revealed hemolysis. Oliguric acute kidney injury developed, and continuous renal replacement therapy had to be applied. On the suspicion of DIIHA, the patient underwent plasmapheresis. Diagnosis was confirmed by a detection of drug-dependent antibody with immune complex formation. Although his hemolysis improved, his liver failure did not improve. He was eventually discharged to palliative care, and subsequently died.

Clinical efficacy of high-flow nasal cannula compared to noninvasive ventilation in patients with post-extubation respiratory failure

BACKGROUND/AIMS: Post-extubation respiratory failure (PERF) is associated with poor clinica l outcomes. High-f low nasa l cannula (HF NC) ox ygen therapy has been used in patients with respiratory failure, but the clinical benefit in patients with PERF remains unclear. The aim of this study was to evaluate the clinical efficacy of HFNC compared to noninvasive ventilation (NIV) in patients with PERF. METHODS: A historic retrospective cohort analysis was performed in 28 beds in the medical Intensive Care Unit (ICU) at a single medical center in South Korea. In total, 73 patients with PERF were enrolled: 39 patients who underwent NIV from April 2007 to March 2009 and 34 patients who received HFNC from April 2009 to May 2011. RESULTS: The rate of avoidance of reintubation was not different between the HFNC group (79.4%) and NIV group (66.7%, p = 0.22). All patients with HFNC tolerated the device, whereas five of those with NIV did not tolerate treatment (p = 0.057). The mean duration of ICU stay was significantly shorter in the HFNC group than in the NIV group (13.4 days vs. 20.6 days, p = 0.015). There was no difference in ICU or in-hospital mortality rate. CONCLUSIONS: HFNC is likely to be as effective as, and better tolerated than, NIV for treatment of PERF.

Effect of Timing of Do-Not-Resuscitate Orders on the Clinical Outcome of Critically Ill Patients / 대한구급학회지

BACKGROUND: Many physicians hesitate to discuss do-not-resuscitate (DNR) orders with patients or family members in critical situations. In the intensive care unit (ICU), delayed DNR decisions could cause unintentional cardiopulmonary resuscitation, patient distress, and substantial cost. We investigated whether the timing of DNR designation affects patient outcome in the medical ICU. METHODS: We enrolled retrospective patients with written DNR orders in a medical ICU (13 bed) from June 1, 2014 to May 31, 2015. The patients were divided into two groups: early DNR patients for whom DNR orders were implemented within 48 h of ICU admission, and late DNR patients for whom DNR orders were implemented more than 48 h after ICU admission. RESULTS: Herein, 354 patients were admitted to the medical ICU and among them, 80 (22.6%) patients had requested DNR orders. Of these patients, 37 (46.3%) had designated DNR orders within 48 hours of ICU admission and 43 (53.7%) patients had designated DNR orders more than 48 hours after ICU admission. Compared with early DNR patients, late DNR patients tended to withhold or withdraw life-sustaining management (18.9% vs. 37.2%, p = 0.072). DNR consent forms were signed by family members instead of the patients. Septic shock was the most common cause of medical ICU admission in both the early and late DNR patients (54.1% vs. 37.2%, p = 0.131). There was no difference in in-hospital mortality (83.8% vs. 81.4%, p = 0.779). Late DNR patients had longer ICU stays than early DNR patients (7.4 ± 8.1 vs. 19.7 ± 19.2, p < 0.001). CONCLUSIONS: Clinical outcomes are not influenced by the time of DNR designation in the medical ICU. The late DNR group is associated with a longer length of ICU stay and a tendency of withholding or withdrawing life-sustaining treatment. However, further studies are needed to clarify the guideline for end-of-life care in critically ill patients.

Extracorporeal Membrane Oxygenation Support in Adult Patients with Hematologic Malignancies and Severe Acute Respiratory Failure / 대한구급학회지

BACKGROUND: Administering extracorporeal membrane oxygenation (ECMO) to critically ill patients with acute respiratory distress syndrome has substantially increased over the last decade, however administering ECMO to patients with hematologic malignancies may carry a particularly high risk. Here, we report the clinical outcomes of patients with hematologic malignancies and severe acute respiratory failure who were treated with ECMO. METHODS: We performed a retrospective review of the medical records of patients with hematologic malignancies and severe acute respiratory failure who were treated with ECMO at the medical intensive care unit of a tertiary referral hospital between March 2010 and April 2015.

Associations between Single Nucleotide Polymorphisms of High Mobility Group Box 1 Protein and Clinical Outcomes in Korean Sepsis Patients

PURPOSE: High mobility group box 1 (HMGB1) plays a central role in the pathogenesis of sepsis and multiple organ dysfunction syndromes. We investigated the associations of a single nucleotide polymorphism (SNP; rs1045411) in HMGB1 with various clinical parameters, severity, and prognosis in patients with sepsis, severe sepsis, or septic shock. MATERIALS AND METHODS: We enrolled 212 adult patients followed for 28 days. All patients were genotyped for rs1045411, and the serum levels of HMGB1 and several cytokines were measured. RESULTS: The proportions of patients according to genotype were GG (71.2%), GA (26.4%), and AA (2.4%). Among patients with chronic lung disease comorbidity, patients with a variant A allele had higher positive blood culture rates and higher levels of various cytokines [interleukin (IL)-1beta, IL-6, IL-10, IL-17, and tumor necrosis factor-alpha] than those with the GG genotype. In the analysis of those with diabetes as a comorbidity, patients with a variant A allele had higher blood culture and Gram-negative culture rates than those with GG genotypes; these patients also had a higher levels of IL-17. In the analysis of those with sepsis caused by a respiratory tract infection, patients with a variant A allele had higher levels of IL-10 and IL-17 (all p<0.05). This polymorphism had no significant impact on patient survival. CONCLUSION: The variant A allele of rs1045411 appears to be associated with a more severe inflammatory response than the GG genotype under specific conditions.

Effect of Timing of Do-Not-Resuscitate Orders on the Clinical Outcome of Critically Ill Patients / 대한중환자의학회지

BACKGROUND: Many physicians hesitate to discuss do-not-resuscitate (DNR) orders with patients or family members in critical situations. In the intensive care unit (ICU), delayed DNR decisions could cause unintentional cardiopulmonary resuscitation, patient distress, and substantial cost. We investigated whether the timing of DNR designation affects patient outcome in the medical ICU. METHODS: We enrolled retrospective patients with written DNR orders in a medical ICU (13 bed) from June 1, 2014 to May 31, 2015. The patients were divided into two groups: early DNR patients for whom DNR orders were implemented within 48 h of ICU admission, and late DNR patients for whom DNR orders were implemented more than 48 h after ICU admission. RESULTS: Herein, 354 patients were admitted to the medical ICU and among them, 80 (22.6%) patients had requested DNR orders. Of these patients, 37 (46.3%) had designated DNR orders within 48 hours of ICU admission and 43 (53.7%) patients had designated DNR orders more than 48 hours after ICU admission. Compared with early DNR patients, late DNR patients tended to withhold or withdraw life-sustaining management (18.9% vs. 37.2%, p = 0.072). DNR consent forms were signed by family members instead of the patients. Septic shock was the most common cause of medical ICU admission in both the early and late DNR patients (54.1% vs. 37.2%, p = 0.131). There was no difference in in-hospital mortality (83.8% vs. 81.4%, p = 0.779). Late DNR patients had longer ICU stays than early DNR patients (7.4 ± 8.1 vs. 19.7 ± 19.2, p < 0.001). CONCLUSIONS: Clinical outcomes are not influenced by the time of DNR designation in the medical ICU. The late DNR group is associated with a longer length of ICU stay and a tendency of withholding or withdrawing life-sustaining treatment. However, further studies are needed to clarify the guideline for end-of-life care in critically ill patients.