Early intubation and decreased in-hospital mortality in patients with coronavirus disease 2019.

BACKGROUND: Some academic organizations recommended that physicians intubate patients with COVID-19 with a relatively lower threshold of oxygen usage particularly in the early phase of pandemic. We aimed to elucidate whether early intubation is associated with decreased in-hospital mortality among patients with novel coronavirus disease 2019 (COVID-19) who required intubation. METHODS: A multicenter, retrospective, observational study was conducted at 66 hospitals in Japan where patients with moderate-to-severe COVID-19 were treated between January and September 2020. Patients who were diagnosed as COVID-19 with a positive reverse-transcription polymerase chain reaction test and intubated during admission were included. Early intubation was defined as intubation conducted in the setting of ≤ 6 L/min of oxygen usage. In-hospital mortality was compared between patients with early and non-early intubation. Inverse probability weighting analyses with propensity scores were performed to adjust patient demographics, comorbidities, hemodynamic status on admission and time at intubation, medications before intubation, severity of COVID-19, and institution characteristics. Subgroup analyses were conducted on the basis of age, severity of hypoxemia at intubation, and days from admission to intubation. RESULTS: Among 412 patients eligible for the study, 110 underwent early intubation. In-hospital mortality was lower in patients with early intubation than those with non-early intubation (18 [16.4%] vs. 88 [29.1%]; odds ratio, 0.48 [95% confidence interval 0.27-0.84]; p = 0.009, and adjusted odds ratio, 0.28 [95% confidence interval 0.19-0.42]; p < 0.001). The beneficial effects of early intubation were observed regardless of age and severity of hypoxemia at time of intubation; however, early intubation was associated with lower in-hospital mortality only among patients who were intubated later than 2 days after admission. CONCLUSIONS: Early intubation in the setting of ≤ 6 L/min of oxygen usage was associated with decreased in-hospital mortality among patients with COVID-19 who required intubation. Trial Registration None.

COVID-19 shares clinical features with anti-melanoma differentiation-associated protein 5 positive dermatomyositis and adult Still's disease.

OBJECTIVES: To investigate the similarities and differences between Coronavirus disease 2019 (COVID-19) and autoimmune and autoinflammatory rheumatic diseases characterised by hyperferritinaemia, such as antimelanoma differentiation-associated protein 5 (MDA5) autoantibody-positive dermatomyositis and adult Still's disease. METHODS: We reviewed consecutive, newly diagnosed, untreated patients with COVID-19, anti-MDA5 dermatomyositis, or adult Still's disease. We compared their clinical, laboratory, and radiological characteristics, including the prevalence of macrophage activation syndrome and lung involvement in each disease. RESULTS: The numbers of patients with COVID-19, anti-MDA5 dermatomyositis, and adult-onset Still's disease with hyperferritinaemia (serum ferritin ≥500ng/dL) who were included for main analysis were 22, 14, and 59, respectively. COVID-19 and adult Still's disease both featured hyperinflammatory status, such as high fever and elevated serum C-reactive protein, whereas COVID-19 and anti-MDA5 dermatomyositis both presented with severe interstitial lung disease and hypoxaemia. While two-thirds of the patients in each group met the criteria for macrophage-activated syndrome that is used in systemic juvenile idiopathic arthritis, the HScore, an indicator of haemophagocytic lymphohistiocytosis, was low in anti-MDA5 dermatomyositis and COVID-19 even in severe or critical cases. The findings of chest computed tomography were similar between COVID-19 and anti-MDA5 dermatomyositis. CONCLUSIONS: COVID-19 shared clinical features with rheumatic diseases characterised by hyperferritinaemia, including anti-MDA5 dermatomyositis and adult Still's disease. These findings should be investigated further in order to shed light on the pathogenesis of not only COVID-19 but also the aforementioned rheumatic diseases.

Cardiac output and stroke volume variation measured by the pulse wave transit time method: a comparison with an arterial pressure-based cardiac output system.

Hemodynamic monitoring is mandatory for perioperative management of cardiac surgery. Recently, the estimated continuous cardiac output (esCCO) system, which can monitor cardiac output (CO) non-invasively based on pulse wave transit time, has been developed. Patients who underwent cardiovascular surgeries with hemodynamics monitoring using arterial pressure-based CO (APCO) were eligible for this study. Hemodynamic monitoring using esCCO and APCO was initiated immediately after intensive care unit admission. CO values measured using esCCO and APCO were collected every 6 h, and stroke volume variation (SVV) data were obtained every hour while patients were mechanically ventilated. Correlation and Bland-Altman analyses were used to compare APCO and esCCO. Welch's analysis of variance, and four-quadrant plot and polar plot analyses were performed to evaluate the effect of time course, and the trending ability. A p-value < 0.05 was considered statistically significant. Twenty-one patients were included in this study, and 143 and 146 datasets for CO and SVV measurement were analyzed. Regarding CO, the correlation analysis showed that APCO and esCCO were significantly correlated (r = 0.62), and the bias ± precision and percentage error were 0.14 ± 1.94 (L/min) and 69%, respectively. The correlation coefficient, bias ± precision, and percentage error for SVV evaluation were 0.4, - 3.79 ± 5.08, and 99%, respectively. The time course had no effects on the biases between CO and SVV. Concordance rates were 80.3 and 75.7% respectively. While CO measurement with esCCO can be a reliable monitor after cardiovascular surgeries, SVV measurement with esCCO may require further improvement.

Interaction between anesthetic conditioning and ischemic preconditioning on metabolic function after hepatic ischemia-reperfusion in rabbits.

BACKGROUND: Both anesthetic-induced and ischemic preconditioning are protective against hepatic ischemia-reperfusion injury. However, the effects of these preventive methods on the metabolic function remain to be elucidated. We investigated the anesthetic conditioning and ischemic preconditioning on the metabolic function of the rabbit model of hepatic ischemia-reperfusion. METHODS: After approval by the institutional animal care and use committee, 36 Japanese White rabbits underwent partial hepatic ischemia for 90 min either under sevoflurane or propofol anesthesia. All the rabbits underwent 90 min of hepatic ischemia, and half of the rabbits in each group underwent additional 10-min ischemia and 10-min reperfusion before index ischemia. Hepatic microvascular blood flow was intermittently measured during reperfusion period, and galactose clearance, serum aminotransferase activities, and lactate concentrations were determined 180 min after reperfusion. RESULTS: Neither anesthetic conditioning with sevoflurane nor ischemic preconditioning altered hepatic microvascular blood flow during reperfusion and serum transaminase activities after reperfusion. However, galactose clearance of reperfused liver was significantly higher under sevoflurane anesthesia than propofol (0.016 ± 0.005/min vs. 0.011 ± 0.004/min). Statistically significant interaction between anesthetic choice and application of ischemic preconditioning suggests that the ischemic preconditioning is selectively protective under propofol anesthesia. Increase of blood lactate concentration was significantly suppressed under sevoflurane anesthesia compared to propofol (1.5 ± 0.8 vs. 3.9 ± 1.4 mmol/l) without any statistically significant interaction with the application of ischemic preconditioning. CONCLUSION: Sevoflurane attenuated the decrease of galactose clearance and increase of the blood lactate after reperfusion compared to propofol. Application of ischemic preconditioning was significantly protective under propofol anesthesia.

Evaluation of the site specificity of acute disuse muscle atrophy developed during a relatively short period in critically ill patients according to the activities of daily living level: A prospective observational study.

INTRODUCTION: In critically ill patients, excessive bed rest and immobilisation have been shown to cause disuse muscle atrophy, which contributes to prolonged hospitalisation and decreased activity of daily living (ADL) levels. However, the degree and site specificity of acute disuse muscle atrophy in critically ill patients during a relatively short intensive care unit (ICU) stay have not been fully elucidated. METHODS: Critically ill patients, who required bed rest on ICU admission, were eligible for this study. The degree of skeletal muscle atrophy was evaluated on the day of, and 72 and 144h after ICU admission by measuring the limb circumference in ADL-dependent or -independent patients separately at five different sites: the midpoint of the upper limb between the acromion and the olecranon, the maximum diameter of the triceps surae in the lower leg, and three different sites in the thigh at 5, 10, and 15cm above the superior pole of the patella. Value of the limb circumference was presented as a percentage relative to the baseline (median). RESULTS: In ADL-dependent patients, limb circumferences at all five sites were decreased significantly at 144h compared with the baseline (98.9-100% in the upper limbs, 97.1-97.2% in the lower legs, and 96.5-99.1% in the thighs), but not at 72h. In contrast, the limb circumferences at almost all sites decreased significantly at both 72 and 144h (100% in the upper limbs, 94.5-94.7% in the lower legs, and 89.7-94.7% in the thighs), compared with the baseline in ADL-independent patients. Muscle atrophy was greater at the four different lower-limb sites compared to the upper limb during 144h in the ICU in the ADL-independent, but not in the ADL-dependent patients. CONCLUSIONS: Compared to ADL-dependent patients, ADL-independent patients are prone to develop muscle weakness, especially in the lower limbs.

[Anesthesia for total hip arthroplasty in a patient with C1 inhibitor deficiency].

C1 inhibitor (INH) deficiency is characterized by the presence of angioedema of the extremities, face, airway and the gastrointestinal tract. Airway obstruction is the most common cause of mortality. A 78-year-old woman presented with repeated episodes of angioedema. These episodes were triggered by general anesthesia, dental extraction, venipuncture, vaccination and loxoprofen. The familiy history of similar symptoms was negative. C1 inhibitor concentrate was administered perioperatively for prophylaxis of attacks. Operation was performed under neurolept anesthesia and combined spinal-epidural anesthesia in order to avoid airway manipulation. Postoperative pain was controlled by patient-controlled epidural anesthesia to prevent attacks triggered by pain. The patient had angioedema on both lower extremities perioperatively but did not develop further attacks. Anesthesia was safely performed in a patient with C1 inhibitor deficiency scheduled for total hip arthroplasty.

Atrial natriuretic peptide reduces hepatic ischemia-reperfusion injury in rabbits.

PURPOSE: Atrial natriuretic peptide (ANP) has been known to be protective against hepatic ischemia/reperfusion injury. The purpose of this study was to verify the hypothesis that ANP conserves microvascular circulation and reduces ischemia-reperfusion injury in the in vivo rabbit model. METHODS: With IRB approval, 30 male Japanese white rabbits under pentobarbital anesthesia were studied. These animals were randomly assigned to the following three groups (n = 10 each): control, ANP, and sham group. Animals in the ANP group received continuous infusion of ANP at 0.1 µg/kg/min throughout the study period. Animals in control and ANP groups underwent 90 min of partial hepatic ischemia by clamping the right hepatic artery and portal vein. Descending aortic blood flow (AoF) was monitored with a transit-time ultrasound flowmeter. Hepatic tissue microvascular blood flow (HTBF) at both right (ischemic) and left (nonischemic) lobe was intermittently evaluated with the hydrogen clearance method. After 180 min of reperfusion, hepatic injury was determined with serum AST and ALT. Galactose clearance of reperfused right lobe was also measured as an indicator of hepatic metabolic function. Histopathological change and the number of apoptotic hepatocytes were also evaluated. RESULTS: Systemic hemodynamic data including mean arterial pressure, heart rate, and AoF did not differ among the three groups during the study period. ANP attenuated ischemia-induced right HTBF decrease. ANP also suppressed histopathological degeneration, apoptosis, and decline in galactose clearance after reperfusion. CONCLUSIONS: ANP attenuated hepatic microvascular dysfunction and hepatocyte injury after reperfusion without significant hemodynamic change.

Transient hemodynamic change and accuracy of arterial blood pressure-based cardiac output.

BACKGROUND: The purpose of this study was to determine the effects of transient arterial blood pressure change on the accuracy of the FloTrac™/Vigileo™ monitor (Edwards Lifesciences, Irvine, CA). METHODS: We compared stroke volume determined with the FloTrac/Vigileo with Doppler during anesthetic induction in 20 patients undergoing abdominal aortic reconstruction. RESULTS: The difference between the FloTrac measurements of stroke volume and the Doppler measurements of stroke volume was -7.5 ± 20.5 mL (mean ± SD) before induction, 0.3 ± 14.9 before laryngoscopy, 17.5 ± 26.9 during laryngoscopy, 20.5 ± 27.6, and -4.5 ± 16.4 mL 3 minutes after endotracheal tube placement. CONCLUSION: The FloTrac/Vigileo measured stroke volume with reasonable accuracy during transient hypotension but overestimated stroke volume during transient hypertension.

The real-time reverse transcription-polymerase chain reaction threshold cycle values for severe acute respiratory syndrome coronavirus 2 predict the prognosis of coronavirus disease 2019 pneumonia.

The clinical course of coronavirus disease 2019 (COVID-19) varies from mild to critical. We retrospectively examined whether clinical and laboratory findings on admission could predict COVID-19 prognosis. Among various factors associated with COVID-19 severity, our results indicated that the real-time reverse transcription-polymerase chain reaction (RT-PCR) threshold cycle (Ct) values for severe acute respiratory syndrome coronavirus 2 were the most useful predictor of COVID-19 prognosis.

Retraction Note: Desflurane anesthesia worsens emergence agitation in adult patients undergoing thyroid surgery compared to sevoflurane anesthesia.

The Editor-in-Chief has retracted this article [1]. The ethics committee approval was granted for an observational study and the need for patient consent was waived. However, the study design described is a randomized controlled trial and therefore patient consent should have been obtained. All authors agree with this retraction.

Can mixed venous hemoglobin oxygen saturation be estimated using a NICO monitor?

BACKGROUND: We hypothesized that mixed venous hemoglobin oxygen saturation (SvO2) can be estimated by calculation from CO2 production, cardiac output, and arterial oxygen saturation measured using a noninvasive cardiac output (NICO) monitor (Novametrix-Respironics, Wallingford, CT). METHODS: Twenty-three patients undergoing aortic aneurysm repair underwent SvO2 monitoring using a pulmonary artery catheter and cardiac output monitoring using a NICO monitor. The estimated SvO2 value calculated from NICO monitor-derived values was compared with the SvO2 value measured using a pulmonary artery catheter. The accuracy of this estimation was analyzed with Bland-Altman method. The ability of this estimation to track the change of SvO2 was also evaluated using correlation analysis to compare the changes of estimated SvO2 and measured SvO2. RESULTS: The bias +/- limits of agreement of the estimated SvO2 against measured SvO2 was -2.1% +/- 11.2%. The change of estimated SvO2 was modestly correlated with the change of measured SvO2. CONCLUSIONS: SvO2 derived from the values measured by the NICO monitor cannot be used interchangeably with the values measured spectrophotometrically using the pulmonary artery catheter. More refinement is required to obtain more reliable estimate of SvO2 less invasively. However, large changes of SvO2 may be detected with this method and can be used as a precautionary sign when the balance between oxygen supply and demand is compromised without inserting a central venous catheter.

Improved accuracy of cardiac output estimation by the partial CO2 rebreathing method.

OBJECTIVE: This study investigated the accuracy of the NICO monitor equipped with the newer software. Additionally, the effects of the increased dead space produced by the NICO monitor on ventilatory settings were investigated. METHODS: Forty-two patients undergoing elective aortic reconstruction participated in this prospective, observational study at a university hospital. Cardiac output was continuously monitored using both the NICO monitor and continuous cardiac output (CCO) measured by a pulmonary artery catheter. A NICO monitor equipped with ver. 4.2 software was used for the first 21 patients while a NICO monitor equipped with ver. 5.0 software was used for the rest of the patients. Cardiac output measured by bolus thermodilution (BCO) at 30 min intervals was used as a reference. RESULTS: The bias +/- precision of the NICO monitor was 0.18 +/- 0.88 l/min with ver. 4.2 software (n = 182) and 0.18 +/- 0.83 l/min with 5.0 software (n = 194). The accuracy of the NICO monitor is comparable to CCO, whose bias +/- precision against BCO is 0.19 +/- 0.81 l/min (n = 376). At the same level of CO(2) production and minute ventilation, PaCO(2) was lower in the patients monitored by NICO with ver. 5.0 software than patients with ver. 4.2 software. CONCLUSIONS: This study demonstrated the improved performance of the NICO monitor with updated software. The performance of the NICO monitor with ver. 4.2 or later software is similar to CCO. However, the cardiac output measurement did not fulfill the criteria of interchangeability to the cardiac output measurement by bolus thermodilution. Updates to ver. 5.0 attenuated the effects of rebreathing introduced by the NICO monitor without compromising the accuracy of the cardiac output measurement.

Difference in autologous blood transfusion-induced inflammatory responses between acute normovolemic hemodilution and preoperative donation.

PURPOSE: The inflammatory response triggered by transfusion is implicated in the pathophysiology of transfusion-related immunomodulation. The authors hypothesized that two distinctive autotransfusion methods, acute normovolemic hemodilution (ANH) and preoperative donation (PD), have different influences on both inflammatory mediator generation during storage and the inflammatory response after a transfusion. The purpose of this study was to compare the plasma concentrations of neutrophil elastase (NE), interleukin (IL)-6, IL-8, and IL-10 in patients who underwent either of these two autologous transfusion methods. METHODS: With institutional review board approval, the plasma concentrations of the above inflammatory mediators were determined in 23 patients with ANH and 8 patients with PD at the following time points: after anesthetic induction, at the end of the operation, and the morning of postoperative day 1. The concentrations of these inflammatory mediators were also measured in the donated blood obtained by either ANH or PD before retransfusion. RESULTS: The mean storage durations were 3.7 h and 6.1 days for ANH and PD, respectively. Higher concentrations of NE and IL-10 were detected in the PD blood than in the ANH blood. Long duration of storage and/or low temperature may have been responsible for the increased NE and IL-10 concentrations in the PD blood. However, the difference between the two groups in the extent of increased plasma concentrations of these inflammatory mediators was not statistically significant. CONCLUSION: Inflammatory mediators were significantly increased in PD blood during storage compared to the blood obtained by ANH. However, their effects on the inflammatory response elicited in the recipients were not significantly different.

One-lung ventilation in a patient with Fontan circulation undergoing diaphragmatic plication surgery: a case report.

BACKGROUND: Surgeries requiring one-lung ventilation (OLV) in patients with Fontan circulation pose great challenges. However, little information is available regarding the safety of OLV in Fontan patients when hemidiaphragmatic paralysis is present. CASE PRESENTATION: A 41-year-old woman who underwent repeated Fontan procedures was re-admitted to our hospital because of worsening shortness of breath. As left hemidiaphragmatic paralysis was considered to be contributing to her symptom, an open thoracic left diaphragmatic plication surgery was scheduled. A preoperative pulmonary artery angiogram revealed a remarkably reduced blood flow to the left lung. The surgeon requested OLV during the surgery. Despite our concern regarding the impact of OLV on the Fontan circulation, OLV did not result in major hemodynamic changes. CONCLUSION: OLV can be safely implemented in patients with hemidiaphragmatic paralysis with preserved Fontan circulation. Preoperative pulmonary artery angiography may provide useful information for estimating the impact of OLV on the Fontan circulation.

Evaluation of the Safety of Percutaneous Dilational Tracheostomy Compared with Surgical Tracheostomy in the Intensive Care Unit.

BACKGROUND: Tracheostomy is a necessary procedure for patients who require long-term mechanical ventilation support. There are two methods for tracheostomy in current use: surgical tracheostomy (ST) and percutaneous dilational tracheostomy (PDT). In the current study, we retrospectively compared the safety of both procedures performed in our intensive care unit (ICU). METHODS: In this study, we enrolled subjects who underwent tracheostomy in our ICU between January 2012 and March 2016. We excluded subjects who were <20 years old and underwent tracheostomy in the operating room. As a primary outcome, we evaluated the rate of complications between ST and PDT groups. The length of ICU stay, time to tracheostomy from intubation, and the rate of mechanical ventilation and mortality at 28 postoperative days were also examined as secondary outcomes. RESULTS: Compared with the ST group, the rate of all complications was lower in the PDT group (13.4% vs. 38.8%, p=0.007). Although the rate of intraoperative complications did not differ between the two groups (3.8% vs. 8.1%, p=0.62), relative to the ST procedure, the PDT procedure was associated with fewer postoperative complications (34.6% vs. 9.6%, p=0.003). Among postoperative complications, accidental removal of the tracheostomy tube and an air leak from the tracheostomy fistula were less frequent in the PDT group than the ST group. Between the two groups, there were no significant differences in their secondary outcomes. CONCLUSION: This retrospective study indicates that relative to ST, PDT is a safer procedure to be performed in the ICU. Fewer postoperative complications following PDT might be attributed to the small skin incision made during this procedure.

Beta-Blocker Therapy Preserves Normal Splenic T-Lymphocyte Numbers Reduced in Proportion to Sepsis Severity in a Sepsis Model.

Lymphocyte cell death contributes to sepsis-induced immunosuppression, leading to poor prognosis. This study examined whether sepsis severity and beta-blocker therapy could affect the degree of T-lymphocyte cell death in a mouse model of sepsis. In the first control study, 20 animals were allocated to 4 groups: control group with sham operation (group C, n = 5) and 3 groups with cecum ligation and puncture (CLP) performed at 3 different sites: proximal, middle, and distal cecum (groups CLP-P, CLP-M, and CLP-D, respectively; n = 5 in each group). Their spleens were resected under general anesthesia 24 hours after CLP, and the total number of normal splenic T lymphocytes per mouse and the percentage of apoptotic T lymphocytes were evaluated using flow cytometry. In the second experimental study, the effect of the beta-blocker esmolol was examined in CLP-P (group CLP-PE vs. CLP-P; n = 5 in each group). The total normal splenic T-lymphocyte numbers per mouse significantly decreased in proportion to CLP severity (group C, 18.6 × 106 (15 × 106-23.6 × 106); CLP-D, 9.2 × 106 (8.8 × 106-9.8 × 106); CLP-M, 6.7 × 106 (6.3 × 106-7.0 × 106); and CLP-P, 5.3 × 106 (5.1 × 106-6.8 × 106)). Beta-blocker therapy restored T-lymphocyte numbers (group CLP-PE vs. CLP-P; 6.94 ± 1.52 × 106 vs. 4.18 ± 1.71 × 106; p=0.027) without affecting apoptosis percentage. Beta-blocker therapy might improve sepsis-induced immunosuppression via normal splenic T-lymphocyte preservation.

Cesarean hysterectomy in a hybrid operating room for placenta percreta: a report of three cases.

BACKGROUND: Placenta percreta is the most severe abnormality in invasive placenta and often treated with cesarean hysterectomy. Endovascular embolization for placental abnormality is known to reduce bleeding from the placental bed and from the abnormal neovasculature surrounding the uterus. We describe three cases of placenta percreta treated with uninterrupted cesarean hysterectomy and embolization performed using a hybrid operating room (HOR). CASE DESCRIPTION: Cases were two placenta previa percretas and an impending uterine rupture with placenta percreta, treated with elective cesarean hysterectomy in HOR. Planned conversion of spinal to general anesthesia was performed after the fetal delivery. Immediate embolic devascularization of abnormal neovasculature was directly observed and facilitated adhesiolysis. Surgical blood losses were 1850 g, 2500 g, and 1180 g, respectively. CONCLUSION: Cesarean hysterectomy combined with endovascular embolization in the HOR for placenta percreta is an advantageous option to enhance patient safety by multidisciplinary approach without patient transfer.

Haptoglobin-2 variant increases susceptibility to acute respiratory distress syndrome during sepsis.

Acute respiratory distress syndrome (ARDS) is an inflammatory lung disorder that frequently complicates critical illness and commonly occurs in sepsis. Although numerous clinical and environmental risk factors exist, not all patients with risk factors develop ARDS, raising the possibility of genetic underpinnings for ARDS susceptibility. We have previously reported that circulating cell-free hemoglobin (CFH) is elevated during sepsis, and higher levels predict worse outcomes. Excess CFH is rapidly scavenged by haptoglobin (Hp). A common HP genetic variant, HP2, is unique to humans and is common in many populations worldwide. HP2 haptoglobin has reduced ability to inhibit CFH-mediated inflammation and oxidative stress compared with the alternative HP1. We hypothesized that HP2 increases ARDS susceptibility during sepsis when plasma CFH levels are elevated. In a murine model of sepsis with elevated CFH, transgenic mice homozygous for Hp2 had increased lung inflammation, pulmonary vascular permeability, lung apoptosis, and mortality compared with wild-type mice. We then tested the clinical relevance of our findings in 496 septic critically ill adults, finding that HP2 increased ARDS susceptibility after controlling for clinical risk factors and plasma CFH. These observations identify HP2 as a potentially novel genetic ARDS risk factor during sepsis and may have important implications in the study and treatment of ARDS.

Anaphylactic Reactions to Native and Light-Exposed Sugammadex Suggested by Basophil Activation Test: A Report of 2 Cases.

We describe 2 patients who developed anaphylactic shock after sugammadex administration during anesthesia. Both had no history of prior sugammadex administration. The serum tryptase concentrations were elevated after the allergic reaction. Basophil activation testing 1 month after the events was positive for sugammadex in 1 patient, and negative in the other. However, it was positive for light-exposed sugammadex solution in both patients, suggesting a possible allergic reaction to a denatured compound of sugammadex generated by light exposure of the sugammadex solution.

Cell-free hemoglobin promotes primary graft dysfunction through oxidative lung endothelial injury.

Primary graft dysfunction (PGD) is acute lung injury within 72 hours of lung transplantation. We hypothesized that cell-free hemoglobin (CFH) contributes to PGD by increasing lung microvascular permeability and tested this in patients, ex vivo human lungs, and cultured human lung microvascular endothelial cells. In a nested case control study of 40 patients with severe PGD at 72 hours and 80 matched controls without PGD, elevated preoperative CFH was independently associated with increased PGD risk (odds ratio [OR] 2.75, 95%CI, 1.23-6.16, P = 0.014). The effect of CFH on PGD was magnified by reperfusion fraction of inspired oxygen (FiO2) ≥ 0.40 (OR 3.41, P = 0.031). Isolated perfused human lungs exposed to intravascular CFH (100 mg/dl) developed increased vascular permeability as measured by lung weight (CFH 14.4% vs. control 0.65%, P = 0.047) and extravasation of Evans blue-labeled albumin dye (EBD) into the airspace (P = 0.027). CFH (1 mg/dl) also increased paracellular permeability of human pulmonary microvascular endothelial cell monolayers (hPMVECs). Hyperoxia (FiO2 = 0.95) increased human lung and hPMVEC permeability compared with normoxia (FiO2 = 0.21). Treatment with acetaminophen (15 µg/ml), a specific hemoprotein reductant, prevented CFH-dependent permeability in human lungs (P = 0.046) and hPMVECs (P = 0.037). In summary, CFH may mediate PGD through oxidative effects on microvascular permeability, which are augmented by hyperoxia and abrogated by acetaminophen.