Effects of inhaled nitric oxide in COVID-19-induced ARDS - Is it worthwhile?

BACKGROUND: Changes in pulmonary hemodynamics and ventilation/perfusion were proposed as hallmarks of Coronavirus disease 2019 (COVID-19)-induced acute respiratory distress syndrome (ARDS). Inhaled nitric oxide (iNO) may overcome these issues and improve arterial oxygenation. METHODS: We retrospectively analyzed arterial oxygenation and pulmonary vasoreactivity in seven COVID-19 ARDS patients receiving 20 ppm iNO for 15-30 minutes. RESULTS: The inhalation of NO significantly improved oxygenation. All patients with severe ARDS had higher partial pressures of oxygen and reduced pulmonary vascular resistance. Significant changes in pulmonary shunting were not observed. CONCLUSION: Overall, iNO could provide immediate help and delay respiratory deterioration in COVID-19-induced moderate to severe ARDS.

Pumpless Extracorporeal Hemadsorption Technique: A New Method for Early Cytokine Elimination?

In recent years, extracorporeal hemadsorption (HA) techniques capable of adsorbing pro- and anti-inflammatory cytokines are increasingly used in various clinical situations. The therapeutic benefit of cytokine elimination likely depends on timing. Although treatment seems to be most effective when started within the first 24 h, therapy is often delayed as it must be combined with another extracorporeal circuit. Thus, using a pumpless extracorporeal HA technique might be a valuable option in order to expedite the commencement of cytokine elimination in critically ill patients.

[Extracorporeal cardiopulmonary resuscitation (eCPR) for out-of-hospital cardiac arrest (OHCA) : Retrospective analysis of a load and go strategy under the aspect of golden hour of eCPR]. / Extrakorporale kardiopulmonale Reanimation (eCPR) bei prähospitalem Herz-Kreislauf-Stillstand (OHCA) : Retrospektive Analyse einer "Load-and-go"-Strategie unter dem Aspekt "golden hour of eCPR".

BACKGROUND: Survival rates after an out-of-hospital cardiac arrest (OHCA) remain low. Extracorporeal cardiopulmonary resuscitation (eCPR) has been introduced as an attempt to increase survival in selected patients and observational studies have shown promising results. Nevertheless, inclusion criteria and timing of eCPR remain undefined. OBJECTIVE: The current study analyzed a load and go strategy with respect to the golden hour of eCPR as a cut-off time for survival and favorable neurological outcome. MATERIAL AND METHODS: This retrospective cohort study included 32 patients who underwent eCPR treatment due to an OHCA between January 2017 and September 2019. Routinely taken patient demographic data (age, BMI, sex) were analyzed. The main focus was set on processing times in the preclinical and clinical setting. Time intervals including OHCA until ambulance arrival, time on scene, transportation times and door to eCPR were extracted from emergency medical service (EMS) and resuscitation protocols. Low-flow times, survival and neurological outcome were analyzed. RESULTS: The use of eCPR in OHCA was associated with survival to hospital discharge in 28% and a good neurological outcome in 19% of the cases. Both groups (survivor and nonsurvivor) did not differ in patient demographics except for age. Survivors were significantly younger (47 (30-60) vs. 59 (50-68) years, p = 0.035). Processing times as well as low-flow times were not significantly different (OHCA-eCPR survivor 64 (50-87) vs. non-survivor 74 (51-85) min; p-value 0.64); however, median low-flow times were outside the golden hour of eCPR (69 (52-86)). CONCLUSION: Despite low-flow times of more than 60 min, eCPR was associated with survival in 28% after OHCA. Hence, exceeding the golden hour of eCPR cannot act as a definitive exclusion criterion for eCPR.

[Update Extracorporeal Lung Support]. / Organersatzverfahren: Update Lungenersatzverfahren.

Extracorporeal lung support is increasingly implemented worldwide in clinical practice in patients with severe acute respiratory distress syndrome (ARDS) and is required when mechanical ventilation is unable to establish sufficient pulmonary gas exchange or if the respirator settings are persistent elevated with an increased risk for ventilator induced lung injury (VILI). Besides that, hypercapnic respiratory failure in patients with acute exacerbation of COPD (AECOPD) or acute respiratory syndrome (ARDS) is common and may require extracorporeal elimination of carbon dioxide by ECCO2R, which also has been increasingly used in the clinical setting. For both therapeutic regimes there is up to date no clear evidence for a significant reduction in mortality in patients with ARDS. Therefore extracorporeal lung support should be still considered as a rescue therapy. In this review, based on a selective literature research and clinical experience of the authors, management of patients with extracorporeal lung assist, focusing on ECMO and ECCO2R is summarized.

Genome-wide association study of myocardial infarction, atrial fibrillation, acute stroke, acute kidney injury and delirium after cardiac surgery - a sub-analysis of the RIPHeart-Study.

BACKGROUND: The aim of our study was the identification of genetic variants associated with postoperative complications after cardiac surgery. METHODS: We conducted a prospective, double-blind, multicenter, randomized trial (RIPHeart). We performed a genome-wide association study (GWAS) in 1170 patients of both genders (871 males, 299 females) from the RIPHeart-Study cohort. Patients undergoing non-emergent cardiac surgery were included. Primary endpoint comprises a binary composite complication rate covering atrial fibrillation, delirium, non-fatal myocardial infarction, acute renal failure and/or any new stroke until hospital discharge with a maximum of fourteen days after surgery. RESULTS: A total of 547,644 genotyped markers were available for analysis. Following quality control and adjustment for clinical covariate, one SNP reached genome-wide significance (PHLPP2, rs78064607, p = 3.77 × 10- 8) and 139 (adjusted for all other outcomes) SNPs showed promising association with p < 1 × 10- 5 from the GWAS. CONCLUSIONS: We identified several potential loci, in particular PHLPP2, BBS9, RyR2, DUSP4 and HSPA8, associated with new-onset of atrial fibrillation, delirium, myocardial infarction, acute kidney injury and stroke after cardiac surgery. TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov NCT01067703, prospectively registered on 11 Feb 2010.

A Multicenter Trial of Remote Ischemic Preconditioning for Heart Surgery.

BACKGROUND: Remote ischemic preconditioning (RIPC) is reported to reduce biomarkers of ischemic and reperfusion injury in patients undergoing cardiac surgery, but uncertainty about clinical outcomes remains. METHODS: We conducted a prospective, double-blind, multicenter, randomized, controlled trial involving adults who were scheduled for elective cardiac surgery requiring cardiopulmonary bypass under total anesthesia with intravenous propofol. The trial compared upper-limb RIPC with a sham intervention. The primary end point was a composite of death, myocardial infarction, stroke, or acute renal failure up to the time of hospital discharge. Secondary end points included the occurrence of any individual component of the primary end point by day 90. RESULTS: A total of 1403 patients underwent randomization. The full analysis set comprised 1385 patients (692 in the RIPC group and 693 in the sham-RIPC group). There was no significant between-group difference in the rate of the composite primary end point (99 patients [14.3%] in the RIPC group and 101 [14.6%] in the sham-RIPC group, P=0.89) or of any of the individual components: death (9 patients [1.3%] and 4 [0.6%], respectively; P=0.21), myocardial infarction (47 [6.8%] and 63 [9.1%], P=0.12), stroke (14 [2.0%] and 15 [2.2%], P=0.79), and acute renal failure (42 [6.1%] and 35 [5.1%], P=0.45). The results were similar in the per-protocol analysis. No treatment effect was found in any subgroup analysis. No significant differences between the RIPC group and the sham-RIPC group were seen in the level of troponin release, the duration of mechanical ventilation, the length of stay in the intensive care unit or the hospital, new onset of atrial fibrillation, and the incidence of postoperative delirium. No RIPC-related adverse events were observed. CONCLUSIONS: Upper-limb RIPC performed while patients were under propofol-induced anesthesia did not show a relevant benefit among patients undergoing elective cardiac surgery. (Funded by the German Research Foundation; RIPHeart ClinicalTrials.gov number, NCT01067703.).

Antifactor Xa Activity for the Management of Anticoagulation during Cardiac Surgery.

Background In patients with autoimmune diseases associated with antiphospholipid antibodies, precise management of anticoagulation during extracorporeal circulation (ECC) is complicated. It was the aim of the present study to determine whether antifactor Xa (aXa) activity is useful in guiding heparin therapy during ECC. Methods In 15 patients undergoing cardiac surgery, anticoagulation with unfractionated heparin (UFH) and its reversal with protamine were guided using activated clotting time (ACT) (>400 second during ECC; ≤100 second for UFH reversal). For each ACT, the corresponding aXa activity levels were measured. Results A total of 144 blood samples were obtained. ACT and aXa activity were significantly correlated (r = 0.771, p< 0.0001, Spearman rank-order correlation). Using receiver operating characteristic curve (ROC) analyses, the cutoffvalues for aXa activity were 1.14 IU/mL (area under the ROC curve [AUC]: 0.89; inaccuracy rate: 9.4%) to predict ACT > 400 seconds and 0.55 IU/mL (AUC: 0.85; inaccuracy rate: 13.3%) for ACT ≤ 100 seconds. Conclusion AXa activity is strongly correlated with ACT, and therefore may be feasible for managing anticoagulation with UFH during ECC.

Multiple electrode aggregometry for the assessment of acquired platelet dysfunctions during extracorporeal circulation.

BACKGROUND: There have been many reports on how the usage of extracorporeal circulation (ECC) is independently associated with the induction of platelet dysfunctions. The aim of the present investigation was to study the capability of the multiple electrode aggregometry (MEA) using the Multiplate (Roche AG, Grenzach, Germany) device to reflect the extent of ECC-associated platelet dysfunctions. PATIENTS AND METHODS: The study population consisted of patients who were treated with either hypothermic (cardiopulmonary bypass [CPB]) or normothermic (extracorporeal membrane oxygenation) ECC. Hemostatic analyses included conventional laboratory coagulation tests and aggregometric measures following stimulation with different agonists using MEA. The area under the aggregation curve in the ADPtest (ex vivo adenosine diphosphate induced platelet aggregation) of the MEA was defined as the primary end point. The analyses were performed before the usage of ECC (baseline) and 90 minutes (T1), 120 minutes (T2), 150 minutes (T3), and 180 minutes (T4) after the usage of ECC. In the hypothermic ECC group, additional hemostatic analyses were performed after the patient's postoperative admission to the intensive care unit (T5). Periprocedural data and results of other hemostatic testing were defined as secondary end points. RESULTS: A total of n = 40 patients were assessed for eligibility and n = 25 patients were finally enrolled into the study (hypothermic ECC group: n = 20; normothermic ECC group: n = 5). The extent of ADP-induced platelet aggregation decreased significantly between baseline and consecutive measuring points during hypothermic ECC and remained unchanged between T4 and T5. In the normothermic ECC group, ADP-induced aggregability was significantly lower at T1 compared with baseline and remained unchanged from T1 onward. CONCLUSION: Data from the present study indicate that ex vivo ADP-induced platelet aggregation in MEA reflects the time-dependent extent of ECC-induced platelet dysfunction.

Real-time measurement of rectal mucosal microcirculation during cardiopulmonary bypass.

OBJECTIVES: Mesenteric ischemia is still a fatal event after cardiac procedures. No adequate intraoperative methods are available to monitor the gastrointestinal mucosal microcirculation in real-time conditions. The aim of the study was to assess a newly designed microprobe using laser Doppler flowmetry and remission spectroscopy. DESIGN: One-group, prospective, nonrandomized, open, pilot diagnostic study. SETTING: Monocenter university hospital. PARTICIPANTS: 50 patients (n = 38 males, 67±6 years) scheduled for cardiopulmonary bypass (CPB) were prospectively included. INTERVENTION: During anesthetic induction, the transrectal microprobe (30×15 mm) was positioned between the inferior and middle rectal valve (5-8 cm). Time periods were summarized at T1 = pre-CPB, T2 = CPB, T3 = post-CPB. MEASUREMENTS AND MAIN RESULTS: In 39 of 50 patients, data recruitment with the microprobe was successful. Measurement failures were due to fecal contaminations and probe dislocations. Rectal blood flow and velocity significantly decreased after bypass initiation (T2). Lowest flow rates were recorded after cross-clamp removal and did not recover at the end of bypass (T3). No side effects of the probe were noted. CONCLUSIONS: The new microprobe allows reproducible, safe, intraoperative, real-time evaluation of the rectal mucosal microcirculation. It could be a useful diagnostic tool to prevent mesenteric ischemia by optimizing extracorporeal circulation in future studies. However, first correlation of rectal blood flow and postoperative events (eg, ischemia, lactate) in a large cohort are necessary.

Remote ischaemic preconditioning for heart surgery. The study design for a multi-center randomized double-blinded controlled clinical trial--the RIPHeart-Study.

AIMS: Transient ischaemia of non-vital tissue has been shown to enhance the tolerance of remote organs to cope with a subsequent prolonged ischaemic event in a number of clinical conditions, a phenomenon known as remote ischaemic preconditioning (RIPC). However, there remains uncertainty about the efficacy of RIPC in patients undergoing cardiac surgery. The purpose of this report is to describe the design and methods used in the "Remote Ischaemic Preconditioning for Heart Surgery (RIPHeart)-Study". METHODS: We are conducting a prospective, randomized, double-blind, multicentre, controlled trial including 2070 adult cardiac surgical patients. All types of surgery in which cardiopulmonary bypass is used will be included. Patients will be randomized either to the RIPC group receiving four 5 min cycles of transient upper limb ischaemia/reperfusion or to the control group receiving four cycles of blood pressure cuff inflation/deflation at a dummy arm. The primary endpoint is a composite outcome (all-cause mortality, non-fatal myocardial infarction, any new stroke, and/or acute renal failure) until hospital discharge. CONCLUSION: The RIPHeart-Study is a multicentre trial to determine whether RIPC may improve clinical outcome in cardiac surgical patients.

[The Helsinki Declaration for Patient Safety in Anaesthesiology--preoperative assessment and preparation]. / Deklaration von Helsinki zur Patientensicherheit in der Anästhesiologie - Teil 6: Präoperative Evaluation und Vorbereitung.

The Helsinki Declaration offers guidelines for the warranty and improvement of patient safety in Anaesthesiology. The assessment of elective patients and their preoperative optimization plays a key role herein. Individual risk factors and preexisting pathologies have to be identified in order to initiate specific pre- and aftercare and an appropriate monitoring. The measures need to be evidence-based, goal-oriented and efficient. Our recommendations aim at elective adult patients planned for non-cardiac and non-lung-resecting surgery and stress the importance of gathering information from patients, performing physical examinations and arranging further diagnostic customized upon these findings only in contrast to routine testing. They shall spark the formulation or improvement of center-based, interdisciplinary standards of procedure in order to fulfill our great responsibility for the perioperative care of our patients.

First Use of a New Extracorporeal Membrane Oxygenation System in COVID19-Associated Adult Respiratory Distress Syndrome: The MobyBox Device.

In late 2020, during the second wave of COVID-19 in Germany, we started using the MobyBox, which is a novel fully pneumatically driven ECMO device, on a regular basis to meet the increasing demand for ECMO therapy. In this case series, we performed a retrospective chart review of seven patients with severe COVID-19-related acute respiratory distress syndrome (ARDS) requiring veno-venous (vv)-ECMO support with the MobyBox. During ECMO treatments we have observed no disadvantages in comparison to conventional ECMO systems. There were no system failures or adverse events directly attributable to the MobyBox system. Our data support that providing vv-ECMO with the MobyBox device is safe and feasible. Furthermore, our findings suggest that the MobyBox device might represent an advantage in terms of biocompatibility. Therefore, more data on this issue is needed to better understand how the pneumatically driven pump affects cellular blood components.

Injection of Recombinant Tissue Plasminogen Activator into Extracorporeal Membrane Oxygenators Postpones Oxygenator Exchange in COVID-19.

Coronavirus disease 2019 (COVID-19) has drastically increased the number of patients requiring extracorporeal life support. We investigate the efficacy and safety of low-dose recombinant tissue-type plasminogen activator (rtPA) injection into exhausted oxygenators to delay exchange in critically ill COVID-19 patients on veno-venous extracorporeal membrane oxygenation (V-V ECMO). Small doses of rtPA were injected directly into the draining section of a V-V ECMO circuit. We compared transmembrane pressure gradient, pump head efficiency, membrane arterial partial oxygen pressure, and membrane arterial partial carbon dioxide pressure before and after the procedure. Bleeding was compared with a matched control group of 20 COVID-19 patients on V-V ECMO receiving standard anticoagulation. Four patients received 16 oxygenator instillations with rtPA at 5, 10, or 20 mg per dose. Administration of rtPA significantly reduced transmembrane pressure gradient (Δ pm = 54.8 ± 18.1 mmHg before vs . 38.3 ± 13.3 mmHg after, p < 0.001) in a dose-dependent manner (Pearson's R -0.63, p = 0.023), allowing to delay oxygenator exchange, thus reducing the overall number of consumed oxygenators. rtPA increased blood flow efficiency η (1.20 ± 0.28 ml/revolution before vs . 1.24 ± 0.27 ml/r, p = 0.002). Lysis did not affect membrane blood gases or systemic coagulation. Minor bleeding occurred in 2 of 4 patients (50%) receiving oxygenator lysis as well as 19 of 20 control patients (95%). Lysis of ECMO oxygenators effectively delays oxygenator exchange, if exchange is indicated by an increase in transmembrane pressure gradient. Application of lysis did not result in higher bleeding incidences compared with anticoagulated patients on V-V ECMO for COVID-19.

Pumpless Extracorporeal Hemadsorption Technique (pEHAT): A Proof-of-Concept Animal Study.

Background: Extracorporeal hemadsorption eliminates proinflammatory mediators in critically ill patients with hyperinflammation. The use of a pumpless extracorporeal hemadsorption technique allows its early usage prior to organ failure and the need for an additional medical device. In our animal model, we investigated the feasibility of pumpless extracorporeal hemadsorption over a wide range of mean arterial pressures (MAP). Methods: An arteriovenous shunt between the femoral artery and femoral vein was established in eight pigs. The hemadsorption devices were inserted into the shunt circulation; four pigs received CytoSorb® and four Oxiris® hemadsorbers. Extracorporeal blood flow was measured in a range between mean arterial pressures of 45-85 mmHg. Mean arterial pressures were preset using intravenous infusions of noradrenaline, urapidil, or increased sedatives. Results: Extracorporeal blood flows remained well above the minimum flows recommended by the manufacturers throughout all MAP steps for both devices. Linear regression resulted in CytoSorb® blood flow [mL/min] = 4.226 × MAP [mmHg] - 3.496 (R-square 0.8133) and Oxiris® blood flow [mL/min] = 3.267 × MAP [mmHg] + 57.63 (R-square 0.8708), respectively. Conclusion: Arteriovenous pumpless extracorporeal hemadsorption resulted in sufficient blood flows through both the CytoSorb® and Oxiris® devices over a wide range of mean arterial blood pressures and is likely an intriguing therapeutic option in the early phase of septic shock or hyperinflammatory syndromes.

Respiratory Physiology of COVID-19 and Influenza Associated Acute Respiratory Distress Syndrome.

Background: There is ongoing debate whether lung physiology of COVID-19-associated acute respiratory distress syndrome (ARDS) differs from ARDS of other origin. Objective: The aim of this study was to analyze and compare how critically ill patients with COVID-19 and Influenza A or B were ventilated in our tertiary care center with or without extracorporeal membrane oxygenation (ECMO). We ask if acute lung failure due to COVID-19 requires different intensive care management compared to conventional ARDS. Methods: 25 patients with COVID-19-associated ARDS were matched to a cohort of 25 Influenza patients treated in our center from 2011 to 2021. Subgroup analysis addressed whether patients on ECMO received different mechanical ventilation than patients without extracorporeal support. Results: Compared to Influenza-associated ARDS, COVID-19 patients had higher ventilatory system compliance (40.7 mL/mbar [31.8-46.7 mL/mbar] vs. 31.4 mL/mbar [13.7-42.8 mL/mbar], p = 0.198), higher ventilatory ratio (1.57 [1.31-1.84] vs. 0.91 [0.44-1.38], p = 0.006) and higher minute ventilation at the time of intubation (mean minute ventilation 10.7 L/min [7.2-12.2 L/min] for COVID-19 vs. 6.0 L/min [2.5-10.1 L/min] for Influenza, p = 0.013). There were no measurable differences in P/F ratio, positive end-expiratory pressure (PEEP) and driving pressures (ΔP). Respiratory system compliance deteriorated considerably in COVID-19 patients on ECMO during 2 weeks of mechanical ventilation (Crs, mean decrease over 2 weeks -23.87 mL/mbar ± 32.94 mL/mbar, p = 0.037) but not in ventilated Influenza patients on ECMO and less so in ventilated COVID-19 patients without ECMO. For COVID-19 patients, low driving pressures on ECMO were strongly correlated to a decline in compliance after 2 weeks (Pearson's R 0.80, p = 0.058). Overall mortality was insignificantly lower for COVID-19 patients compared to Influenza patients (40% vs. 48%, p = 0.31). Outcome was insignificantly worse for patients requiring veno-venous ECMO in both groups (50% mortality for COVID-19 on ECMO vs. 27% without ECMO, p = 0.30/56% vs. 34% mortality for Influenza A/B with and without ECMO, p = 0.31). Conclusion: The pathophysiology of early COVID-19-associated ARDS differs from Influenza-associated acute lung failure by sustained respiratory mechanics during the early phase of ventilation. We question whether intubated COVID-19 patients on ECMO benefit from extremely low driving pressures, as this appears to accelerate derecruitment and consecutive loss of ventilatory system compliance.

COVID-19 Induced Acute Respiratory Distress Syndrome-A Multicenter Observational Study.

Background: Proportions of patients dying from the coronavirus disease-19 (COVID-19) vary between different countries. We report the characteristics; clinical course and outcome of patients requiring intensive care due to COVID-19 induced acute respiratory distress syndrome (ARDS). Methods: This is a retrospective, observational multicentre study in five German secondary or tertiary care hospitals. All patients consecutively admitted to the intensive care unit (ICU) in any of the participating hospitals between March 12 and May 4, 2020 with a COVID-19 induced ARDS were included. Results: A total of 106 ICU patients were treated for COVID-19 induced ARDS, whereas severe ARDS was present in the majority of cases. Survival of ICU treatment was 65.0%. Median duration of ICU treatment was 11 days; median duration of mechanical ventilation was 9 days. The majority of ICU treated patients (75.5%) did not receive any antiviral or anti-inflammatory therapies. Venovenous (vv) ECMO was utilized in 16.3%. ICU triage with population-level decision making was not necessary at any time. Univariate analysis associated older age, diabetes mellitus or a higher SOFA score on admission with non-survival during ICU stay. Conclusions: A high level of care adhering to standard ARDS treatments lead to a good outcome in critically ill COVID-19 patients.

Successful fast track protocol implementation for patients undergoing transapical transcatheter aortic valve implantation.

BACKGROUND: The aim of the current study is to report our experience with fast-track treatment of patients undergoing transapical transcatheter aortic valve implantation (TA-TAVI) and to determine perioperative predictors for fast-track protocol failure. METHODS: Being one of the pioneering centers to start performing TA-TAVI back in 2005, we routinely included patients undergoing this procedure into our fast-track management program since 2008. Between January 2008 and June 2013, 207 consecutive high-risk patients (mean age 79 ± 7 years, mean Log. EuroSCORE 24 ± 10) who underwent TA-TAVI accordingly to our institutional fast-track approach were prospectively collected and analyzed. Uni- and multivariate analysis were performed to identify independent pre- and perioperative predictors of fast-track protocol failure, defined as inability to discharge the patient from the intensive care unit (ICU) on the day of surgery or as readmission to the ICU 48 h after the initial discharge. RESULTS: Fast-track management was successful in 83 % of the patients. 30-day mortality was 8 %. Fast-track protocol failure (17 %) was associated with an outcome worsening compared to the remaining patients (mortality: 40 % vs. 2 % and mean hospital stay: 19 ± 12 vs. 10 ± 9 days; P = .002). Independent predictors of fast-track protocol failure were age ≥85 years (OR 3.1; CI 95 % 1.89-6.21), ejection fraction (EF) ≤30 % (OR 2.6; CI 95 % 1.99-7.52), moderate to severe preoperative mitral valve regurgitation (OR 2.7; CI 95 % 1.27-6.43) and fluoroscopy time ≥12 min (OR 2.9; CI 95 % 1.28-7.46). CONCLUSIONS: Fast-track patient management following TA-TAVI is safe and reproducible in the majority of patients. Besides patient-related preoperative risk factors (age ≥85 years, EF ≤30 % and moderate to severe preoperative mitral valve regurgitation) a technically challenging intraoperative course as evidenced in a prolonged fluoroscopy time are independent predictors of fast-track protocol failure which is associated with high loss of patient outcome.

Use of lidocaine in endotracheal intubation. Blood and urine concentrations in patients and deceased after unsuccessful resuscitation.

In toxicological analysis of postmortem samples the local anesthetic lidocaine is often identified. In most cases, lidocaine levels result from its use as aid in endotracheal intubation. The range of the drug's concentration in blood and urine was studied under controlled conditions from a cohort of cardiac surgery patients (n=35). Plasma concentrations 1 h after exposure to lidocaine in the range of the recommended 81 mg coating the endotracheal tube were less than 0.2 mg/l, its metabolite monoethylglycinxylidide (MEGX) less than 0.05 mg/l (median ratio 0.18, range 0.03-1.23). Also the concentrations of lidocaine and MEGX in urine samples were low (less than 1.2 and 0.1 mg/l, respectively) with MEGX/lidocaine ratios of 0.11 (median, range up to 1.2). These data were compared with results obtained by analyzing postmortem blood and urine samples of 18 deceased with a documented cardiopulmonary resuscitation attempt prior to death. Blood concentrations were in the same range (lidocaine median 0.07, range 0.02-1.07 mg/l; MEGX median 0.01, range <0.001-0.044 mg/l); besides low lidocaine concentrations in urine. MEGX was detected only in 2 out of 9 urine samples. The results of the present study confirm that lidocaine is absorbed in the trachea from the endotracheal tube coated with lidocaine containing gel. Postmortem quantitative results can be explained on the basis of the data obtained in the controlled study.

Early postoperative serum cystatin C predicts severe acute kidney injury following cardiac surgery: a post-hoc analysis of a randomized controlled trial.

OBJECTIVE: Acute kidney injury (AKI) after cardiac surgery procedures is associated with poor patient outcomes. Cystatin C as a marker for renal failure has been shown to be of prognostic value; however, a wide range of its predictive accuracy has been reported. The aim of the study was to evaluate whether the measurement of pre- and postoperative serum cystatin C improves the prediction of AKI. METHODS: In a single-centre, prospective study of 70 patients (74 ± 9 ys; range 47-85 ys; 77% male), cystatin C was measured six times: (T1=preoperative, T2=start cardiopulmonary bypass (CPB), T3=20 min after CPB, T4=end of operation; T5=24 h postoperatively; T6=7d postoperatively). Predictive property, in terms of the need for renal replacement therapy (RRT), was analysed by receiver operating characteristics (ROC) statistics and described by the area under the curve (AUC). RESULTS: With respect to RRT (n=8), serum cystatin C was significantly higher at the end of the operation (T4), 24 h postoperatively at T5 and at T6. The AUCs for preoperative T1 and intraoperative T2/3 cystatin C were <0.7 (95% CI, 0.47-0.85). The earliest significant predictive AUCs were found at the end of the operation (T4: p=0.03 95% CI 0.58-0.88 AUC 0.73) and 24 h postoperatively (T5: p=0.003 95% CI 0.74-0.96 AUC 0.85). CONCLUSIONS: Early postoperative serum cystatin C increase appears to be a moderate biomarker in the prediction of AKI, whereas a preoperative and intraoperative cystatin C increase has only a limited diagnostic and predictive value.