Impairment of Inspiratory Muscle Function after COVID-19.

BACKGROUND: Persistent symptoms after acute coronavirus-disease-2019 (COVID-19) are common, and there is no significant correlation with the severity of the acute disease. In long-COVID (persistent symptoms >4 weeks after acute COVID-19), respiratory symptoms are frequent, but lung function testing shows only mild changes that do not explain the symptoms. Although COVID-19 may lead to an impairment of the peripheral nervous system and skeletal muscles, respiratory muscle function has not been examined in this setting. METHODS: In this study, we assessed the severity of dyspnea (NYHA-function class) in long-COVID patients and analyzed its association with body mass index (BMI), FEV1, forced vital capacity, other parameters of body plethysmography, diffusing capacity for carbon monoxide (DLCO), arterial blood gases, and inspiratory muscle function, assessed by airway occlusion pressure (P0.1) and maximal inspiratory pressure (PImax) in two respiratory clinics in Germany between Oct 2020 and Aug 2021. RESULTS: A total of 116 patients were included in the study. The mean age was 50.2 ± 14.5 years; BMI, 26.7 ± 5.87 kg/m2; NYHA class I, 19%; II, 27%; III, 41%; and IV, 14%. While lung function values and computed tomography or conventional X-ray of the chest were in the normal range, inspiratory muscle function was markedly impaired. P01 was elevated to 154 ± 83%predicted and PImax was reduced to 41 ± 25%predicted. PImax reduction was strongly associated with the severity of dyspnea but independent of BMI, time after acute COVID-19 and most of the other parameters. CONCLUSIONS: This study shows that in long-COVID patients, respiratory symptoms may be mainly caused by reduced inspiratory muscle strength. Assessment of PImax and P0.1 might better explain dyspnea than classical lung function tests and DLCO. A prospective study is needed to confirm these results.

Generalizable items and modular structure for computerised physician staffing calculation on intensive care units.

Intensive care medicine remains one of the most cost-driving areas within hospitals with high personnel costs. Under the scope of limited budgets and reimbursement, realistic needs are essential to justify personnel staffing. Unfortunately, all existing staffing models are top-down calculations with a high variability in results. We present a workload-oriented model, integrating quality of care, efficiency of processes, legal, educational, controlling, local, organisational and economic aspects. In our model, the physician's workload solely related to the intensive care unit depends on three tasks: Patient-oriented tasks, divided in basic tasks (performed in every patient) and additional tasks (necessary in patients with specific diagnostic and therapeutic requirements depending on their specific illness, only), and non patient-oriented tasks. All three tasks have to be taken into account for calculating the required number of physicians. The calculation tool further allows to determine minimal personnel staffing, distribution of calculated personnel demand regarding type of employee due to working hours per year, shift work or standby duty. This model was introduced and described first by the German Board of Anesthesiologists and the German Society of Anesthesiology and Intensive Care Medicine in 2008 and since has been implemented and updated 2012 in Germany. The modular, flexible nature of the Excel-based calculation tool should allow adaption to the respective legal and organizational demands of different countries. After 8 years of experience with this calculation, we report the generalizable key aspects which may help physicians all around the world to justify realistic workload-oriented personnel staffing needs.

Generalizable items of quantitative and qualitative cornerstones for personnel requirement of physicians in anesthesia.

Anesthesiologists perform a broad spectrum of tasks. However, in many countries, there is no legal basis for personnel staffing of physicians in anesthesia. Also, the German diagnosis related groups system for refunding does not deliver such a basis. Thus, in 2006 a new calculation base for the personnel requirement that included an Excel calculation sheet was introduced by the German Board of Anesthesiologists (BDA) and the German Society of Anesthesiology and Intensive Care Medicine (DGAI), and updated in 2009 and 2015. Oriented primarily to organizational needs, in 2015, BDA/DGAI defined quantitative and qualitative cornerstones for personnel requirement of physicians in anesthesia, especially reflecting recent laws governing physician's working conditions and competence in the field of anesthesia, as well as demands of strengthened legal rights of patients, patient care and safety. We present a workload-oriented model, integrating core working hours, shift work or standby duty, quality of care, efficiency of processes, legal, educational, controlling, local, organizational and economic aspects for calculating personnel demands. Auxiliary tables enable physicians to calculate personnel demands due to differing employee workload, non-patient oriented tasks and reimbursement of full-equivalents due to parental leave, prohibition of employment, or long-term illness. After 10 years of experience with the first calculation tool, we report the generalizable key aspects and items of a necessary calculation tool which may help physicians to justify realistic workload-oriented personnel staffing demands in anesthesia. A modular, flexible nature of a calculation tool should allow adaption to the respective legal and organizational demands of different countries.

Early echocardiographic detection of a massive intracardiac thrombus in a patient scheduled for orthotopic liver transplantation.

Transesophageal echocardiography (TEE) in cases of orthotopic liver transplantation is gaining acceptance for intraoperative hemodynamic monitoring. The timepoint of TEE probe insertion varies and is based on the fear of bleeding complications in the setting of portal hypertension with esophageal varices. In this case, early insertion of the TEE probe and examination resulted in the early detection of a large intracardiac thrombus, and thus the cancellation of the planned procedure. This case highlights the potential value of early TEE examination in orthotopic liver transplantation.

Superimposed high-frequency jet ventilation combined with continuous positive airway pressure/assisted spontaneous breathing improves oxygenation in patients with H1N1-associated ARDS.

BACKGROUND: Numerous cases of swine-origin 2009 H1N1 influenza A virus (H1N1)-associated acute respiratory distress syndrome (ARDS) bridged by extracorporeal membrane oxygenation (ECMO) therapy have been reported; however, complication rates are high. We present our experience with H1N1-associated ARDS and successful bridging of lung function using superimposed high-frequency jet ventilation (SHFJV) in combination with continuous positive airway pressure/assisted spontaneous breathing (CPAP/ASB). METHODS: We admitted five patients with H1N1 infection and ARDS to our intensive care unit. Although all patients required pure oxygen and controlled ventilation, oxygenation was insufficient. We applied SHFJV/CPAP/ASB to improve oxygenation. RESULTS: Initial PaO2/FiO2 ratio prior SHFJV was 58-79 mmHg. In all patients, successful oxygenation was achieved by SHFJV (PaO2/FiO2 ratio 105-306 mmHg within 24 h). Spontaneous breathing was set during first hours after admission. SHFJV could be stopped after 39, 40, 72, 100, or 240 h. Concomitant pulmonary herpes simplex virus (HSV) infection was observed in all patients. Two patients were successfully discharged. The other three patients relapsed and died within 7 weeks mainly due to combined HSV infection and in two cases reoccurring H1N1 infection. CONCLUSIONS: SHFJV represents an alternative to bridge lung function successfully and improve oxygenation in the critically ill.

The neuronal guidance protein netrin-1 reduces alveolar inflammation in a porcine model of acute lung injury.

INTRODUCTION: Acute lung injury (ALI) is an inflammatory disorder of pulmonary or extrapulmonary origin. We have previously demonstrated that netrin-1 dampens murine ALI, and in an attempt to advance this finding into future clinical practice we evaluated whether netrin-1 would reduce alveolar inflammation during porcine ALI. METHODS: This was a controlled in vivo experimental study in pigs. We induced ALI through lipoploysaccharide (LPS) infusion (50 µg/kg) for 2 hours. Following this, we exposed animals to either vehicle, intravenous netrin-1 (netrin-1 i.v.) or inhaled netrin-1 (netrin-1 inh.). Serum samples and bronchoalveolar lavage (BAL) were obtained to determine levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, interleukin-6 and interleukin-8 at baseline and 6 hours following treatment. Myeloperoxidase activity (MPO) and protein levels were determined in the BAL, and tissue samples were obtained for histological evaluation. Finally, animals were scanned with spiral CT. RESULTS: Following LPS infusion, animals developed acute pulmonary injury. Serum levels of TNF-α and IL-6 were significantly reduced in the netrin-1 i.v. group. BAL demonstrated significantly reduced cytokine levels 6 hours post-netrin-1 treatment (TNF-α: vehicle 633 ± 172 pg/ml, netrin-1 i.v. 84 ± 5 pg/ml, netrin-1 inh. 168 ± 74 pg/ml; both P < 0.05). MPO activity and protein content were significantly reduced in BAL samples from netrin-1-treated animals. Histological sections confirmed reduced inflammatory changes in the netrin-1-treated animals. Computed tomography corroborated reduced pulmonary damage in both netrin-1-treated groups. CONCLUSIONS: We conclude that treatment with the endogenous anti-inflammatory protein netrin-1 reduces pulmonary inflammation during the initial stages of ALI and should be pursued as a future therapeutic option.

Bbeta15-42 (FX06) reduces pulmonary, myocardial, liver, and small intestine damage in a pig model of hemorrhagic shock and reperfusion.

OBJECTIVE: The fibrin-derived peptide Bbeta15-42 (also called FX06) has been shown to reduce myocardial infarct size following ischemia/reperfusion. Hemorrhagic shock (HS) followed by volume resuscitation represents a similar scenario, whereby a whole organism is vulnerable to reperfusion injury. DESIGN: We subjected male farm-bred landrace pigs ( approximately 30 kg) to HS by withdrawing blood to a mean arterial pressure of 40 mm Hg for 60 minutes. Pigs were then resuscitated with shed blood and crystalloids for 60 minutes, and at this time, FX06 (2.4 mg/kg, n = 8) or vehicle control (phosphate buffered saline; 2.4 mg/kg, n = 7) was injected as an intravenous bolus. SETTING: University hospital laboratory. SUBJECTS: Anesthetized male farm-bred landrace pigs. MEASUREMENTS AND MAIN RESULTS: Data are presented as mean +/- sd. Five hours after resuscitation, controls presented acute lung injury (Pao2/Fio2-ratio <300 mm Hg; extra-vascular lung water index (marker for lung injury): 9.0 +/- 1.8 mL/kg) and myocardial dysfunction/damage (cardiac index: 4.3 +/- 0.25 L/min/m; stroke volume index: 30 +/- 6 mL/m; cardiac TnT levels: 0.58 +/- 0.25 ng/mL). In contrast, FX06-treated animals showed significantly improved pulmonary and circulatory function (Pao2/Fio2-ratio >*400 mm Hg; extra-vascular lung water index: *5.2 +/- 2.1 mL/kg, cardiac index: *6.3 +/- 1.4 L/min/m; stroke volume index: *51 +/- 11 mL/m; cardiac TnT levels: *0.11 +/- 0.09 ng/mL; *p < 0.05). Also, tissue oxygenation (tpO2; mm Hg) was significantly improved during reperfusion in FX06-treated pigs when compared with controls (liver 51 +/- 4 vs. *65 +/- 4; serosa 44 +/- 5 vs. *55 +/- 7; mucosa 14 +/- 4 vs. *26 +/- 4). Finally, FX06 reduced accumulation of myeloperoxidase-positive cells (mainly neutrophils) in myocardium, liver, and small intestine and reduced interleukin-6 plasma levels (*p < 0.05; compared with controls). CONCLUSION: We conclude that in a pig model of HS and reperfusion, administration of FX06 during reperfusion protects shock- susceptible organs such as heart, lung, liver, and small intestine.

A double blind, single centre, sub-chronic reperfusion trial evaluating FX06 following haemorrhagic shock in pigs.

OBJECTIVE: Haemorrhagic shock causes ischaemia and subsequent fluid resuscitation causes reperfusion injury, jointly resulting in high morbidity and mortality. We tested whether the anti-inflammatory fibrin-derived peptide, Bbeta(15-42), also called FX06, is tissue protective in a model of haemorrhagic shock. METHODS: In a pig model, we standardised the severity of haemorrhagic shock by achieving a cumulative oxygen deficit of approximately 100ml/kg body weight by withdrawing blood over a period of 1h. This was followed by resuscitation with shed blood and full electrolyte solution, and pigs were monitored for 3 days. At reperfusion, 17 pigs were randomly assigned to FX06 or solvent treatment. RESULTS: FX06-treated pigs demonstrated improved cardiac function (stroke volume index: 67ml/m(2) versus 33ml/m(2)), decreased troponin T release in the early reperfusion (0.24ng/ml versus 0.78ng/ml), decreased AST levels after 24h (106U/l versus 189U/l) and decreased creatinine levels after 24h (108micromol/l versus 159micromol/l). Furthermore, FX06-treated pigs demonstrated preservation of the gut/blood barrier, while controls demonstrated high endotoxin plasma levels indicating translocation of bacteria and/or its products (0.2EU/ml versus 24.3EU/ml) after 24h. This study also demonstrates a significantly improved neurological performance in the FX06 group as determined by S100beta serum levels (0.72microg/l versus 1.25microg/l) after 48h and neurological deficit scores (11 versus 70) after 24h. CONCLUSION: FX06 - when administered as an adjunct to fluid resuscitation therapy - is organ protective in pigs. Further investigations are warranted to reveal the protective mechanism of FX06.

Successful transtracheal lung ventilation using a manual respiration valve: an in vitro and in vivo study.

BACKGROUND: Lung ventilation through a thin transtracheal cannula may be attempted in patients with laryngeal stenosis or "cannot intubate, cannot ventilate" situations. It may be impossible to achieve sufficient ventilation if the lungs are spontaneously emptying only through the thin transtracheal cannula, which imposes high resistance to airflow, resulting in dangerous hyperinflation. Therefore, the authors describe the use of a manual respiration valve that serves as a bidirectional pump providing not only inflation but also active deflation of the lungs in case of emergency transtracheal lung ventilation. METHODS: The effectiveness of such a valve was tested in vitro using mechanical lungs in combination with two different cannula sizes and various gas flows. The valve was then tested in five pigs using a transtracheal 16-gauge cannula with three different combinations of inspiratory/expiratory times and gas flows and an occluded upper airway. RESULTS: In the mechanical lungs, the valve permitted higher minute volumes compared with spontaneous lung emptying. In vivo, the arterial oxygen and carbon dioxide partial pressures increased initially and then remained stable over 1 h (arterial oxygen tension, 470.8 +/- 86.8; arterial carbon dioxide tension, 63.0 +/- 7.2 mmHg). The inspiratory pressures measured in the trachea remained below 10 cm H2O and did not substantially influence central venous and pulmonary artery pressures. Mean arterial pressure and cardiac output were unaffected by the ventilation maneuvers. CONCLUSIONS: This study demonstrated in vitro and in vivo in adult pigs that satisfactory lung ventilation can be assured with transtracheal ventilation through a 16-gauge cannula for a prolonged period of time if combined with a bidirectional manual respiration valve.

The effects of thoracic epidural anesthesia on hepatic perfusion and oxygenation in healthy pigs during general anesthesia and surgical stress.

Perioperative liver injury due to decreased perfusion may be an underlying mechanism behind the development of systemic inflammatory response syndrome. We designed this animal study to assess whether thoracic epidural anesthesia (TEA) impairs liver oxygenation due to induced hypotension. After ethical approval, 19 anesthetized and acutely instrumented pigs were randomly assigned to 3 groups (control and TEA alone versus TEA plus volume loading). Bupivacaine 0.5% 0.75 mL per segment was injected into the epidural space, aiming for a T5 to T12 block. After baseline values were obtained, measurements were repeated 60 and 120 min after epidural injection. TEA was associated with decreased mean arterial blood pressure but no change in total hepatic blood flow. Oxygen delivery to the liver and oxygen uptake remained unchanged. Liver tissue oxygen partial pressure did not decrease. The plasma indocyanine green disappearance rate remained stable. Volume loading before TEA did not relevantly affect total hepatic blood flow; it even decreased oxygen supply to the liver by hemodilution. We conclude that, despite decreased mean arterial blood pressure, TEA did not affect liver oxygenation. There was no clinically relevant effect of volume loading on total hepatic perfusion.