Tacrolimus Variability and Clinical Outcomes in the Early Post-lung Transplantation Period: Oral Versus Continuous Intravenous Administration.

BACKGROUND AND OBJECTIVE: High variability in tacrolimus pharmacokinetics directly after lung transplantation (LuTx) may increase the risk for acute kidney injury (AKI) and transplant rejection. The primary objective was to compare pharmacokinetic variability in patients receiving tacrolimus orally versus intravenously early after LuTx. METHODS: Pharmacokinetic and clinical data from 522 LuTx patients transplanted between 2010 and 2020 in two university hospitals were collected to compare orally administered tacrolimus to intravenous tacrolimus early post-transplantation. Tacrolimus blood concentration variability, measured as intrapatient variability (IPV%) and  percentage of time within the therapeutic range (TTR%), was analyzed within the first 14 days after LuTx. Secondary outcomes were AKI, acute rejection, length of stay in the intensive care unit (ICU), and mortality in the ICU and during hospital admission. RESULTS: We included 224 patients in the oral and 298 in the intravenous group. The mean adjusted IPV% was 10.8% (95% confidence interval [CI] 6.9-14.6; p < 0.001) higher in the oral group (27.2%) than the intravenous group (16.4%). The mean TTR% was 7.3% (95% CI - 11.3 to - 3.4; p < 0.001) lower in the oral group (39.6%) than in the intravenous group (46.9%). The incidence of AKI was 46.0% for oral and 42.6% for intravenous administration (adjusted odds ratio [OR] 1.2; 95% CI 0.8-1.8; p = 0.451). The frequencies of clinically diagnosed acute rejection in the oral and intravenous groups were nonsignificant (24.6% vs 17.8%; OR 1.5 [95% CI 1.0-2.3; p = 0.059]). ICU and hospital mortality rate and ICU length of stay were similar. CONCLUSIONS: Administering tacrolimus orally directly after LuTx leads to a higher variability in blood concentrations compared to intravenous administration. There was no difference in the occurrence of AKI or transplant rejection.

International Survey on Mechanical Ventilation During Extracorporeal Membrane Oxygenation.

The optimal ventilation strategy for patients on extracorporeal membrane oxygenation (ECMO) remains uncertain. This survey reports current mechanical ventilation strategies adopted by ECMO centers worldwide. An international, multicenter, cross-sectional survey was conducted anonymously through an internet-based tool. Participants from North America, Europe, Asia, and Oceania were recruited from the extracorporeal life support organization (ELSO) directory. Responses were received from 48 adult ECMO centers (response rate 10.6%). Half of these had dedicated ventilation protocols for ECMO support. Pressure-controlled ventilation was the preferred initial ventilation mode for both venovenous ECMO (VV-ECMO) (60%) and venoarterial ECMO (VA-ECMO) (34%). In VV-ECMO, the primary goal was lung rest (93%), with rescue therapies commonly employed, especially neuromuscular blockade (93%) and prone positioning (74%). Spontaneous ventilation was typically introduced after signs of pulmonary recovery, with few centers using it as the initial mode (7%). A quarter of centers stopped sedation within 3 days after ECMO initiation. Ventilation strategies during VA-ECMO focused less on lung-protective goals and transitioned to spontaneous ventilation earlier. Ventilation strategies during ECMO support differ considerably. Controlled ventilation is predominantly used initially to provide lung rest, often facilitated by sedation and neuromuscular blockade. Few centers apply "awake ECMO" early during ECMO support, some utilizing partial neuromuscular blockade.

Cardiogenic shock due to probable SARS-CoV-2 myocarditis-a case report.

Background: Since the start of the COVID-19 pandemic, many case reports have been presented describing different cardiac symptoms due to the SARS-CoV-2 infection. However, severe cardiac failure due to COVID-19 seems to be rare. Case summary: A 30-year-old woman presented with COVID-19 and cardiogenic shock due to a lymphocytic myocarditis. Since she deteriorated under treatment with inotropes, she was referred to our centre, and veno-arterial extracorporeal life support was started. Subsequently, the aortic valve only opened sporadically, and spontaneous contrast appeared in the left ventricle (LV), pointing towards difficulties with unloading LV. Therefore, an Impella for venting the LV was implanted. After 6 days of mechanical circulatory support, her heart function recovered. All support could be weaned, and 2 months later, she had made a full recovery. Discussion: We presented a patient with severe cardiogenic shock due to an acute virus-negative lymphocytic myocarditis associated with a SARS-CoV-2 infection. Since the precise aetiology of SARS-CoV-2-related myocarditis remains to be elucidated and no virus could be detected in the heart, a causal relationship remains speculative.

Incidence and risk factors of deep vein thrombosis after extracorporeal life support.

BACKGROUND: Deep vein thrombosis (DVT) after decannulation of extracorporeal life support (ECLS) is not uncommon. Moreover, the impact of anticoagulation and potential risk factors is unclear. Furthermore, it is unclear if cannula-associated DVT is more common in ECLS patients compared to critically ill patients without ECLS. METHODS: All adult patients who were successfully weaned from ECLS and were screened for DVT following decannulation were included in this observational cohort study. The incidence of post-ECLS-DVT was assessed and the cannula-associated DVT rate was compared with that of patients without ECLS after central venous catheter (CVC) removal. The correlation between the level of anticoagulation, risk factors, and post-ECLS-DVT was determined. RESULTS: We included 30 ECLS patients and 53 non-ECLS patients. DVT was found in 15 patients (50%) of which 10 patients had a DVT in a cannulated vein. No correlation between the level of anticoagulation and DVT was found. V-V ECLS mode was the only independent risk factor for post-ECLS-DVT (OR 5.5; 95%CI 1.16-26.41). We found no difference between the ECLS and non-ECLS cohorts regarding cannula-associated DVT rate (33% vs. 32%). CONCLUSION: Post-ECLS-DVT is a common finding that occurs in half of all patients supported with ECLS. The incidence of cannula-associated DVT was equal to CVC-associated DVT in critically ill patients without ECLS. V-V ECLS was an independent risk factor for post-ECLS-DVT.

Conservative initial postoperative anticoagulation strategy after HeartMate 3 left ventricular assist device implantation.

INTRODUCTION: Although anticoagulation therapy is mandated after implantation of a left ventricular assist device (LVAD), postoperative bleedings and reoperations occur relatively frequently and are associated with worse outcomes. We evaluated the use of a conservative postoperative anticoagulation protocol in patients implanted with a HeartMate 3 (HM3) LVAD. METHODS: In a single-centre retrospective analysis of postoperative outcomes after HM3 LVAD implantation, a standard (old) anticoagulation protocol (i.e. early, full-dose anticoagulation with low-molecular weight heparin and overlapping vitamin K antagonist) was compared with a new conservative anticoagulation protocol (i.e. slow initiation of vitamin K antagonists without overlapping heparin). Main outcomes were changes in international normalised ratio (INR), lactate dehydrogenase (LDH), bleeding and/or tamponade events requiring reoperation, length of stay and adverse events. RESULTS: In total, 73 patients (48 in old vs 25 in new protocol group) were evaluated. Mean age was 56 years (standard deviation 13) and most patients (78%) were males. Changes in INR and LDH in the first 14 days were similar in both groups (p = 0.50 and p = 0.997 for interaction, respectively). Number of bleeding/tamponade events requiring reoperation was lower in the new than in the old protocol group (4% vs 33%, p = 0.005). Postoperative 30-day mortality was similar, and we observed no thromboembolic events. Median (25th-75th percentiles) total length of postoperative hospital stay (27 (25-41) vs 21 (19-27) days, p < 0.001) and length of intensive care unit stay (5 (2-9) vs 2 (2-5) days, p = 0.022) were significantly shorter in the new protocol group. CONCLUSION: These retrospective data suggest that conservative slow initiation of anticoagulation therapy after HM3 LVAD implantation is associated with less bleeding/tamponade events requiring reoperation, a similar safety profile and a shorter duration of stay than the currently advised standard anticoagulation protocol.

Long-term outcome and bridging success of patients evaluated and bridged to lung transplantation on the ICU.

BACKGROUND: Evaluating and bridging patients to lung transplantation (LTx) on the intensive care unit (ICU) remains controversial, especially without a previous waitlist status. Long term outcome data after LTx from ICU remains scarce. We compared long-term survival and development of chronic lung allograft dysfunction (CLAD) in elective and LTx from ICU, with or without previous waitlist status. METHODS: Patients transplanted between 2004 and 2018 in 2 large academic Dutch institutes were included. Long-term survival and development of CLAD was compared in patients who received an elective LTx (ELTx), those bridged and transplanted from the ICU with a previous listing status (BTT), and in patients urgently evaluated and bridged on ICU (EBTT). RESULTS: A total of 582 patients underwent a LTx, 70 (12%) from ICU, 39 BTT and 31 EBTT. Patients transplanted from ICU were younger than ELTx (46 vs 51 years) and were bridged with mechanical ventilation (n = 42 (60%)), extra corporeal membrane oxygenation (n = 28 (40%)), or both (n = 21/28). Bridging success was 48% in the BTT group and 72% in the EBTT group. Patients bridged to LTx on ICU had similar 1 and 5 year survival (86.8% and 78.4%) compared to elective LTx (86.8% and 71.9%). This was not different between the BTT and EBTT group. 5 year CLAD free survival was not different in patients transplanted from ICU vs ELTx. CONCLUSION: Patients bridged to LTx on the ICU with and without prior listing status had excellent short and long-term patient and graft outcomes, and was similar to patients electively transplanted.

Hemorrhagic complications during extracorporeal membrane oxygenation - The role of anticoagulation and platelets.

PURPOSE: Hemorrhagic complications during extracorporeal membrane oxygenation are frequent and have a negative impact on outcome. We studied the association between activated partial thromboplastin time or platelet count and the occurrence of hemorrhagic complications. The secondary objective was to determine risk factors for hemorrhagic complications. METHODS: Retrospective cohort study in a single-center Dutch university hospital. We included all adult patients on extracorporeal membrane oxygenation admitted to the intensive care unit between 2010 and 2017. RESULTS: We included 164 consecutive patients of which 73 (45%) had a hemorrhagic complication. The most prevalent hemorrhagic complications were surgical site (62%) and cannula site bleeding (18%). Survival to discharge was 67% in the patients without a hemorrhagic complication and 33% in the patients with hemorrhagic complications (p < .01). A higher activated partial thromboplastin time in the 24 h prior was associated with the occurrence of hemorrhagic complications (adjusted hazard ratio per 10 s increase 1.14; (95% CI 1.05-1.24). Venoarterial extracorporeal membrane oxygenation, duration of support, and higher activated partial thromboplastin time were risk factors for the occurrence of hemorrhagic complications. CONCLUSIONS: Higher activated partial thromboplastin time is associated with the occurrence of hemorrhagic complications.

Transferring the critically ill patient: are we there yet?

During the past few decades the numbers of ICUs and beds has increased significantly, but so too has the demand for intensive care. Currently large, and increasing, numbers of critically ill patients require transfer between critical care units. Inter-unit transfer poses significant risks to critically ill patients, particularly those requiring multiple organ support. While the safety and quality of inter-unit and hospital transfers appear to have improved over the years, the effectiveness of specific measures to improve safety have not been confirmed by randomized controlled trials. It is generally accepted that critically ill patients should be transferred by specialized retrieval teams, but the composition, training and assessment of these teams is still a matter of debate. Since it is likely that the numbers and complexity of these transfers will increase in the near future, further studies are warranted.

Simulator-based crew resource management training for interhospital transfer of critically ill patients by a mobile ICU.

BACKGROUND: Transporting critically ill ICU patients by standard ambulances, with or without an accompanying physician, imposes safety risks. In 2007 the Dutch Ministry of Public Health required that all critically ill patients transferred between ICUs in different hospitals be transported by a mobile ICU (MICU). Since March 2009 a specially designed MICU and a retrieval team have served the region near University Medical Center Groningen, in the northeastern region of the Netherlands. The MICU transport program includes simulator-based crew resource management (CRM) training for the intensivists and ICU nurses, who, with the drivers, constitute the MICU crews. METHODS: Training entails five pivotal aspects: (1) preparation, (2) teamwork, (3) new equipment, (4) mobility, and (5) safety. For example, the training accustoms participants to working in the narrow, moving ambulance and without benefit of additional manpower. The scenario-based team training, which takes about four hours, occurs in a training facility, with its reconstructed ICU, and then in the MICU itself. A "wireless" patient simulator that is able to mimic hemodynamic and respiratory patterns and to simulate lung and heart sounds is used. All scenarios can be adjusted to simulate medical, logistic, or technical problems. RESULTS: Since the start of MICU training in 2009, more than 70 training sessions, involving 100 team members, have been conducted. Quality issues identified include failure to anticipate possible problems (such as failing to ask for intubation of a respiratory-compromised patient at intake); late responses to alarms of the ventilator, perfusor pump, or monitor; and not anticipating a possible shortage of medication. CONCLUSIONS: Setting up and implementing simulator-based CRM training provides feasible and helpful preparation for an MICU team.

Bedside lung ultrasound in the critically ill patient with pulmonary pathology: different diagnoses with comparable chest X-ray opacification.

The differential diagnosis and treatment of opacifications on the chest X-ray in critically ill patients may be challenging. This holds in particular the patient that suffers from respiratory failure with hemodynamic instability. Opacification in the chest X-ray could be the result of hematothorax, pleural effusion, atelectasis, or consolidation. Physical examination of such patients may not always indicate what the cause of the opacification is and thus may not always help indicate the correct therapeutic approach. In such cases, bedside ultrasound may be very helpful. We present two cases with similar chest X-ray opacifications but different diagnoses established with the help of a bedside lung ultrasound. There is documented accuracy of ultrasound in differentiating pleural effusions from consolidation. Ultrasound is safe and may be an alternative for computed tomography scan in a hemodynamically or respiratory unstable intensive care patient.

Inter-hospital transport of critically ill patients; expect surprises.

INTRODUCTION: Inter-hospital transport of critically ill patients is increasing. When performed by specialized retrieval teams there are less adverse events compared to transport by ambulance. These transports are performed with technical equipment also used in an Intensive Care Unit (ICU). As a consequence technical problems may arise and have to be dealt with on the road. In this study, all technical problems encountered while transporting patients with our mobile intensive care unit service (MICU) were evaluated. METHODS: From March 2009 until August 2011 all transports were reviewed for technical problems. The cause, solution and, where relevant, its influence on protocol were stated. RESULTS: In this period of 30 months, 353 patients were transported. In total 55 technical problems were encountered. We provide examples of how they influenced transport and how they may be resolved. CONCLUSION: The use of technical equipment is part of intensive care medicine. Wherever this kind of equipment is used, technical problems will occur. During inter-hospital transports, without extra personnel or technical assistance, the transport team is dependent on its own ability to resolve these problems. Therefore, we emphasize the importance of having some technical understanding of the equipment used and the importance of training to anticipate, prevent and resolve technical problems. Being an outstanding intensivist on the ICU does not necessarily mean being qualified for transporting the critically ill as well. Although these are lessons derived from inter-hospital transport, they may also apply to intra-hospital transport.

Quality of interhospital transport of the critically ill: impact of a Mobile Intensive Care Unit with a specialized retrieval team.

INTRODUCTION: In order to minimize the additional risk of interhospital transport of critically ill patients, we started a mobile intensive care unit (MICU) with a specialized retrieval team, reaching out from our university hospital-based intensive care unit to our adherence region in March 2009. To evaluate the effects of this implementation, we performed a prospective audit comparing adverse events and patient stability during MICU transfers with our previous data on transfers performed by standard ambulance. METHODS: All transfers performed by MICU from March 2009 until December 2009 were included. Data on 14 vital variables were collected at the moment of departure, arrival and 24 hours after admission. Variables before and after transfer were compared using the paired-sample T-test. Major deterioration was expressed as a variable beyond a predefined critical threshold and was analyzed using the McNemar test and the Wilcoxon Signed Ranks test. Results were compared to the data of our previous prospective study on interhospital transfer performed by ambulance. RESULTS: A total of 74 interhospital transfers of ICU patients over a 10-month period were evaluated. An increase of total number of variables beyond critical threshold at arrival, indicating a worsening of condition, was found in 38 percent of patients. Thirty-two percent exhibited a decrease of one or more variables beyond critical threshold and 30% showed no difference. There was no correlation between patient status at arrival and the duration of transfer or severity of disease. ICU mortality was 28%. Systolic blood pressure, glucose and haemoglobin were significantly different at arrival compared to departure, although significant values for major deterioration were never reached. Compared to standard ambulance transfers of ICU patients, there were less adverse events: 12.5% vs. 34%, which in the current study were merely caused by technical (and not medical) problems. Although mean Acute Physiology and Chronic Health Evaluation II (APACHE II) score was significantly higher, patients transferred by MICU showed less deterioration in pulmonary parameters during transfer than patients transferred by standard ambulance. CONCLUSIONS: Transfer by MICU imposes less risk to critically ill patients compared to transfer performed by standard ambulance and has, therefore, resulted in an improved quality of interhospital transport of ICU patients in the north-eastern part of the Netherlands.