Predictive markers related to local and systemic inflammation in severe COVID-19-associated ARDS: a prospective single-center analysis.

BACKGROUND: As the COVID-19 pandemic strains healthcare systems worldwide, finding predictive markers of severe courses remains urgent. Most research so far was limited to selective questions hindering general assumptions for short- and long-term outcome. METHODS: In this prospective single-center biomarker study, 47 blood- and 21 bronchoalveolar lavage (BAL) samples were collected from 47 COVID-19 intensive care unit (ICU) patients upon admission. Expression of inflammatory markers toll-like receptor 3 (TLR3), heme oxygenase-1 (HO-1), interleukin (IL)-6, IL-8, leukocyte counts, procalcitonin (PCT) and carboxyhemoglobin (CO-Hb) was compared to clinical course. Clinical assessment comprised acute local organ damage, acute systemic damage, mortality and outcome after 6 months. RESULTS: PCT correlated with acute systemic damage and was the best predictor for quality of life (QoL) after 6 months (r = - 0.4647, p = 0.0338). Systemic TLR3 negatively correlated with impaired lung function (ECMO/ECLS: r = - 0.3810, p = 0.0107) and neurological short- (RASS mean: r = 0.4474, p = 0.0023) and long-term outcome (mRS after 6 m: r = - 0.3184, p = 0.0352). Systemic IL-8 correlated with impaired lung function (ECMO/ECLS: r = 0.3784, p = 0.0161) and neurological involvement (RASS mean: r = - 0.5132, p = 0.0007). IL-6 in BAL correlated better to the clinical course than systemic IL-6. Using three multivariate regression models, we describe prediction models for local and systemic damage as well as QoL. CO-Hb mean and max were associated with higher mortality. CONCLUSIONS: Our predictive models using the combination of Charlson Comorbidity Index, sex, procalcitonin, systemic TLR3 expression and IL-6 and IL-8 in BAL were able to describe a broad range of clinically relevant outcomes in patients with severe COVID-19-associated ARDS. Using these models might proof useful in risk stratification and predicting disease course in the future. Trial registration The trial was registered with the German Clinical Trials Register (Trial-ID DRKS00021522, registered 22/04/2020).

Cytokine levels associated with favorable clinical outcome in the CAPSID randomized trial of convalescent plasma in patients with severe COVID-19.

Objectives: To determine the profile of cytokines in patients with severe COVID-19 who were enrolled in a trial of COVID-19 convalescent plasma (CCP). Methods: Patients were randomized to receive standard treatment and 3 CCP units or standard treatment alone (CAPSID trial, ClinicalTrials.gov NCT04433910). The primary outcome was a dichotomous composite outcome (survival and no longer severe COVID-19 on day 21). Time to clinical improvement was a key secondary endpoint. The concentrations of 27 cytokines were measured (baseline, day 7). We analyzed the change and the correlation between serum cytokine levels over time in different subgroups and the prediction of outcome in receiver operating characteristics (ROC) analyses and in multivariate models. Results: The majority of cytokines showed significant changes from baseline to day 7. Some were strongly correlated amongst each other (at baseline the cluster IL-1ß, IL-2, IL-6, IL-8, G-CSF, MIP-1α, the cluster PDGF-BB, RANTES or the cluster IL-4, IL-17, Eotaxin, bFGF, TNF-α). The correlation matrix substantially changed from baseline to day 7. The heatmaps of the absolute values of the correlation matrix indicated an association of CCP treatment and clinical outcome with the cytokine pattern. Low levels of IP-10, IFN-γ, MCP-1 and IL-1ß on day 0 were predictive of treatment success in a ROC analysis. In multivariate models, low levels of IL-1ß, IFN-γ and MCP-1 on day 0 were significantly associated with both treatment success and shorter time to clinical improvement. Low levels of IP-10, IL-1RA, IL-6, MCP-1 and IFN-γ on day 7 and high levels of IL-9, PDGF and RANTES on day 7 were predictive of treatment success in ROC analyses. Low levels of IP-10, MCP-1 and high levels of RANTES, on day 7 were associated with both treatment success and shorter time to clinical improvement in multivariate models. Conclusion: This analysis demonstrates a considerable dynamic of cytokines over time, which is influenced by both treatment and clinical course of COVID-19. Levels of IL-1ß and MCP-1 at baseline and MCP-1, IP-10 and RANTES on day 7 were associated with a favorable outcome across several endpoints. These cytokines should be included in future trials for further evaluation as predictive factors.

Risk Factors for Prolonged Mechanical Ventilation and Delayed Extubation Following Bimaxillary Orthognathic Surgery: A Single-Center Retrospective Cohort Study.

BACKGROUND: Bimaxillary orthognathic surgery bears the risk of severe postoperative airway complications. There are no clear recommendations for immediate postoperative follow-up and monitoring. OBJECTIVE: to identify potential risk factors for prolonged mechanical ventilation and delayed extubation in patients undergoing bimaxillary orthognathic surgery. METHODS: The data of all consecutive patients undergoing bimaxillary surgery between May 2012 and October 2019 were analyzed in a single-center retrospective cohort study. The clinical data were evaluated regarding baseline characteristics and potential factors linked with delayed extubation. RESULTS: A total of 195 patients were included; 54.9% were female, and the median age was 23 years (IQR 5). The median body mass index was 23.1 (IQR 8). Nine patients (4.6%) were of American Society of Anesthesiologists Physical Status Classification System III or higher. The median duration of mechanical ventilation in the intensive care unit was 280 min (IQR, 526 min). Multivariable analysis revealed that premedication with benzodiazepines (odds ratio (OR) 2.60, 95% confidence interval (0.99; 6.81)), the male sex (OR 2.43, 95% confidence interval (1.10; 5.36)), and the duration of surgery (OR 1.54, 95% confidence interval (1.07; 2.23)) were associated with prolonged mechanical ventilation. By contrast, total intravenous anesthesia was associated with shorter ventilation time (OR 0.19, 95% confidence interval (0.09; 0.43)). CONCLUSION: premedication with benzodiazepines, the male sex, and the duration of surgery might be considered to be independent risk factors for delayed extubation in patients undergoing bimaxillary surgery.

Aspirin, heparin and ischemia time in microvascular free flap surgery - their influence and an optimal anticoagulation protocol.

BACKGROUND: Microvascular surgery has become a standardized technique for reconstruction of large tissue defects in Head and Neck Reconstructive Surgery. However, the main dreaded complications are thrombosis of blood vessels or major bleeding after surgery. Several different anticoagulation protocols have been established in the last decades to overcome these problems with varying degrees of success. METHODS: Over a period of six years, a standardized anticoagulation protocol including acetylsalicylic acid (ASA) and unfractionated heparin (UFH) for direct intraoperative and postoperative administration was established, optimized and compared to a previously used non-standardized protocol. A total of 178 flap surgeries were included in the development and optimization process of the protocol. RESULTS: ASA significantly increased the risk of complications when used for longer than 72 h (OR = 2.52; p = 0.002; 95% CI 1.39-4.59). Administration of UFH reduced flap loss (bolus: OR 0.68; p = 0.47; 95% CI 0.24-1.93; continuous UFH administration: OR = 0.61; p = 0.33; 95% CI 0.22-1.66), however doses greater than 500 IU/ h of UFH as continuous infusion increased the risk of complications. Reduction in ischemia time had no effect on the occurrence of complications. CONCLUSION: Anticoagulation regimes in microvascular surgery can influence the postoperative complication rate. The optimal protocol should consist of a combination of ASA and UFH for the intraoperative and direct postoperative phase. Prolonged administration of ASA as well as doses >500 IU/ h of UFH are to be avoided due to the increased complication rate.

Influence of surgical stabilization of clavicle fractures in multiply-injured patients with thoracic trauma.

Thoracic trauma has decisive influence on the outcome of multiply-injured patients and is often associated with clavicle fractures. The affected patients are prone to lung dysfunction and multiple organ failure. A multi-center, retrospective analysis of patient records documented in the TraumaRegister DGU was performed to assess the influence of surgical stabilization of clavicle fractures in patients with thoracic trauma. A total of 3,209 patients were included in the analysis. In 1362 patients (42%) the clavicle fracture was treated operatively after 7.1 ± 5.3 days. Surgically treated patients had a significant reduction in lung failure (p = 0.013, OR = 0.74), multiple organ failure (p = 0.001, OR = 0.64), intubation time (p = 0.004; -1.81 days) and length of hospital stay (p = 0.014; -1.51 days) compared to non-operative treatment. Moreover, surgical fixation of the clavicle within five days following hospital admission significantly reduced the rates of lung failure (p = 0.01, OR = 0.62), multiple organ failure (p = 0.01, OR = 0.59) and length of hospital stay (p = 0.01; -2.1 days). Based on our results, multiply-injured patients with thoracic trauma and concomitant clavicle fracture may benefit significantly from surgical stabilization of a clavicle fracture, especially when surgery is performed within the first five days after hospital admission.

The Role of von Willebrand Factor in Microvascular Surgery in Severely Injured Patients.

Microvascular anastomosis has become a standard surgical technique for reconstruction because of increasing possibilities, indications, and clinical success regarding the survival of the flaps. However, the main dreaded complications exist in thrombosis. Leaving surgical complications aside, systemic problems like disorder of the coagulation-fibrinolysis system are a significant cause of graft loss usually being unrecognized. Reports exist describing a hypercoagulable state with clotting activation and inhibition of fibrinolysis after trauma and delayed surgery considering the secondary homeostasis. In this clinical case, a patient had a large soft tissue defect at the temporal side of the head after severe trauma. After some days of primary stabilization, reconstruction using a free microvascular latissimus dorsi flap was performed. Multiple revisions of the arterial and venous branches had to be performed intraoperatively due to insufficient flap perfusion. After 24 hours, definitive flap loss occurred due to multiple thrombosis in the arterial and venous branches. Postoperative comprehensive coagulation analysis revealed a distinct activation of primary hemostasis with massively increased von Willebrand factor parameters and factor VIII activity as well as acetylsalicylic acid resistance contributing to thrombotic occlusion. In severely injured patients, comprehensive preoperative determination of the coagulation status (especially those of the primary hemostasis) is indispensable before performing free flap reconstruction surgeries to reduce the risk of microvascular flap loss.

Reconstruction of the Mediastinum and Tracheopexy for Tracheomalacia in Straight Back Syndrome.

Tracheomalacia in straight back syndrome results from chronic compression of the trachea and the mainstem bronchi mainly because of decreased mediastinal diameter. The mainstay of correction is the increase of mediastinal space and the restoration of the tracheal lumen and stability. Owing to the great variability of the manifestation of this disease, individualized approaches are required. We describe our approach in a 36-year-old woman with straight back syndrome associated severe tracheobronchomalacia with reconstruction of the proximal aorta, brachiocephalic artery, sternoplasty, and anterior tracheopexy, which resulted in successful treatment of the condition.

Prevent deterioration and long-term ventilation: intensive care following thoracic surgery.

PURPOSE OF REVIEW: Patients with indication for lung surgery besides the pulmonary pathology often suffer from independent comorbidities affecting several other organ systems. Preventing patients from harmful complications due to decompensation of underlying organ insufficiencies perioperatively is pivotal. This review draws attention to the peri- and postoperative responsibility of the anaesthetist and intensivist to prevent patients undergoing lung surgery deterioration. RECENT FINDINGS: During the last decades we had to accept that 'traditional' intensive care medicine implying deep sedation, controlled ventilation, liberal fluid therapy, and broad-spectrum antimicrobial therapy because of several side-effects resulted in prolongation of hospital length of stay and a decline in quality of life. Modern therapy therefore should focus on the convalescence of the patient and earliest possible reintegration in the 'life-before.' Avoidance of sedative and anticholinergic drugs, early extubation, prophylactic noninvasive ventilation and high-flow nasal oxygen therapy, early mobilization, well-adjusted fluid balance and reasonable use of antibiotics are the keystones of success. SUMMARY: A perioperative interprofessional approach and a change in paradigms are the prerequisites to improve outcome and provide treatment for elder and comorbid patients with an indication for thoracic surgery.

Early Postoperative Use of Diuretics After Kidney Transplantation Showed Increase in Delayed Graft Function.

PURPOSE: In acute renal injury, diuretics are widely considered to be harmful. Nevertheless, they are used frequently after kidney transplantation. We hypothesized that diuretics administered in the early postoperative treatment after kidney transplantation increase the incidence of delayed graft function (DGF). METHODS: In this monocentric, retrospective cohort analysis, we screened the closed files of all consecutive patients who underwent kidney transplantation from 2011 to 2017. The outcome variable was DGF, defined as at least 1 hemodialysis within 7 days postoperatively. To stratify for baseline characteristics such as waiting time or cold ischemic period, we employed a propensity score-matched analysis. Further statistical processing included basic descriptive statistics, Mann-Whitney U test, and binary logistic regression analysis. RESULTS: The unmatched cohort included 445 patients and showed a significantly increased rate of DGF for patients who received either furosemide or mannitol or a combination of both (5% vs 25%; P < .001). Mannitol (odds ratio [OR]: 4.094) and furosemide (OR: 2.915) showed a significant correlation with DGF in the multivariate regression analysis. Propensity score-based matching resulted in a matched cohort of 214 patients with balanced baseline risk variables. In this matched cohort, the rate of DGF was significantly increased in patients who received diuretics in the early postoperative treatment (7% vs 16%; P = .031). CONCLUSION: Our results show that postoperatively administered diuretics are associated with an increased rate of DGF even in a cohort with balanced preoperative risk variables. This study supports recently published reviews, which call diuretics in the transplantation process into question.

Protocol based evaluation for feasibility of extubation compared to clinical scoring systems after major oral cancer surgery safely reduces the need for tracheostomy: a retrospective cohort study.

BACKGROUND: Despite risks, complications and negative impact to quality of life, tracheostomy is widely used to bypass upper airway obstruction after major oral cancer surgery (MOCS). Decision to tracheostomy is frequently based on clinical scoring systems which mainly have not been validated by different cohorts. Delayed extubation in the Intensive Care Unit (ICU) may be a suitable alternative in selected cases. We hypothesize that delayed routine ICU extubation after MOCS instead of scoring system based tracheostomy is safe, feasible and leads to lower tracheostomy rates. METHODS: We retrospectively analyzed our clinical protocol which provides routine extubation of patients after MOCS in the ICU. The primary outcome measure was a composite of early reintubation within 24 h or secondary tracheostomy. Secondary outcome measures included airway obstruction related morbidity and mortality. Predictor variables included tumor localisation, surgical procedure and reconstruction method, length of operation and pre-existing morbidity. Furthermore we assessed the ability of four clinical scoring systems to identify patients requiring secondary tracheostomy. Statistical processing includes basic descriptive statistics, Chi-squared test and multivariate logistic regression analysis. RESULTS: Two hundred thirty four cases were enclosed to this retrospective study. Fourteen patients (6%) required secondary tracheostomy, Ten patients (4%) required reintubation within 24 h after extubation. No airway obstruction associated mortality, morbidity and cannot intubate cannot ventilate situation was observed. Seventy five percent of the patients were extubated within 17 h after ICU admission. All evaluated scores showed a poor positive predictive value (0.08 to 0.18) with a sensitivity ranged from 0.13 to 0.63 and specificity ranged from 0.5 to 0.93. CONCLUSIONS: Our data demonstrate that common clinical scoring systems fail to prevent tracheostomy in patients after MOCS. Application of scoring systems may lead to a higher number of unnecessary tracheostomies. Delayed routine extubation in the ICU after MOCS seems an appropriate and safe approach to avoid tracheostomy and the related morbidity.

Outcome and complications after treatment of facial fractures at different times in polytrauma patients.

Finding the correct point of time for operative treatment of facial fractures in multiply injured people remains one of the most important challenges in modern emergency medicine. Findings relating to pathophysiological mechanisms after severe trauma argue against the early operative treatment of non-life-threatening injuries. Our retrospective analysis investigated the effects on complications and outcome of different time points for operative treatment of maxillofacial fractures in multiply injured patients. Over a period of 10 years (2003-2012) we could identify 1543 patients, of whom 553 had fractures of the facial skull. 168 of the facial fracture patients were operated on their fractures, 97 at a time later than 72 h. Despite the delayed time of operation, the patients showed fewer complications (21.6% vs 25.4%). This resulted in fewer additional stays in hospital (9.3% vs 11.3%), and also in fewer plate removals (23.7% vs 33.8%). We conclude that delayed operative fracture treatment does not lead to more complications. The optimal time for operative treatment has to be determined individually as the earliest point at which no adverse effects from comorbidities are expected.

Feasibility of a Supraglottic Airway Device for Transbronchial Lung Cryobiopsy-A Retrospective Analysis.

OBJECTIVES: To determine the feasibility of a supraglottic airway device for transbronchial cryobiopsy in adults. DESIGN: Retrospective analysis of anesthetic and pulmonary records between March 2015 and August 2016. SETTING: Single university medical center. PARTICIPANTS: One hundred thirty-two patients who underwent transbronchial cryobiopsy procedures performed under general anesthesia. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: Failure-free use of a supraglottic airway device was 96.8%. Failure of supraglottic airway device insertion was 3.1% because of impossible placement (n = 1), high oropharyngeal leakage (n = 1), massive bleeding requiring bronchial blocker (n = 1), and acute right heart failure with cardiac arrest requiring resuscitation (n = 1). No serious adverse events due to the supraglottic airway device were observed. CONCLUSION: The data demonstrated that transbronchial cryobiopsy under general anesthesia and airway management with a supraglottic airway device was a feasible technique.

Intra-abdominal pressure, Cardiac Index and vascular resistance during hyperthermic intraperitoneal chemotherapy: a prospective observational study.

BACKGROUND: Increased intra-abdominal pressure and hemodynamic variations during hyperthermic intraperitoneal chemotherapy (HIPEC) are expected to be comparable to pneumoperitoneum with decreased Cardiac Index (CI) and increased Systemic Vascular Resistance Index (SVRI). We hypothesized that despite comparable increased intra-abdominal pressure, hemodynamic changes during HIPEC would substantially differ from those described in laparoscopic surgery. METHODS: In this prospective observational clinical study, after obtaining written informed consent, we assessed intra-abdominal pressure and hemodynamic and respiratory changes during HIPEC in 10 consecutive patients. Intra-abdominal pressure as the primary endpoint was continuously measured with a catheter placed in the abdominal cavity. Secondary endpoints were hemodynamic changes measured by pulse contour analysis and respiratory alterations. Fluid management was based on stroke volume variation. RESULTS: The mean intra-abdominal pressure was constantly elevated during HIPEC at a level of 14.2 mmHg (P=0.002 compared to baseline). The mean SVRI dropped from 1716 dyn*sec/cm³/m² to 1490 dyn*sec/cm5/m² at the end of HIPEC (P<0.05). Mean CI increased from 3.2 to 3.45 L/m² (P<0.001) and Horovitz index decreased from 548 to 380 (P=0.001). Median fluid intake was 7000 mL. No patient developed acute kidney injury. CONCLUSIONS: Increased intra-abdominal pressure during HIPEC was comparable to pneumoperitoneum. Hemodynamic changes however were opposed with a decrease in SVRI and a compensative increase in CI. Current guidelines for anesthetic management in patients undergoing HIPEC are mainly based on findings from laparoscopic surgery and should therefore be reconsidered critically.

Short-term heart and lung support: extracorporeal membrane oxygenation and extracorporeal life support.

In the last few years, progress in engineering has helped to develop minimized systems for extracorporeal membrane oxygenation and circulatory support. However, despite progress in engineering, the use of these systems still requires a trained team with special skills to be a beneficial and safe tool in the care of critically ill patients. The described indications and proceedings are based on the daily experience of the Freiburg group using these systems both on site in our own hospital and for transport purposes from primary care hospitals into our center of maximum care. The aim of this review is to share our hands-on experience in urgent/emergent implantations and therefore contribute to the knowledge within the growing community of users in this specialized field of extracorporeal support.

Prospective model-based comparison of different laryngoscopes for difficult intubation in infants.

BACKGROUND: Difficult intubation in infants is uncommon but may be a challenge for the anesthesiologist. Many optical-assisted techniques are available to ease endotracheal placement of tube but have not been systemically evaluated for pediatric practice. AIM: The study was performed to compare conventional pediatric Macintosh - with different optical laryngoscopes in difficult endotracheal intubation in infants. We hypothesized that inexperienced anesthetists would perform more successful with optical devices and that differences between the devices would be found. METHODS/MATERIALS: In this randomized controlled study, 30 anesthesia residents performed endotracheal intubation in an infant model of difficult airway presenting with airway obstruction and neck immobilization. Primary endpoints were intubation success rate and intubation time. Beyond that glottis view, dental trauma and difficulty of technique were evaluated and measured by a study observer. Macintosh, Airtraq(®), Storz DCI(®) -, and Gyrus Infant Bullard(®) laryngoscopes were used in random order. After standardized briefing every resident had three attempts of at most 120 s with every device to place a 3-mm tube into the trachea. Glottis view and difficulty of technique were rated by the residents using classification of Cormack/Lehane and Visual Analogue Scale (VAS; 0 = easy to 10 = very difficult). RESULTS: Success rate was 41% with conventional Macintosh, 43% with Airtraq(®), 62% with Storz DCI(®), and 100% with Bullard(®) laryngoscopes. Median time from passing the lips to first ventilation was 67 s (Storz DCI(®) laryngoscope), 54 s (Macintosh laryngoscope), 45 s (Airtraq(®) laryngoscope), and 21 s (Bullard(®) laryngoscope), respectively. Dental trauma did not occur with Bullard(®) laryngoscope and was frequent with Storz DCI(®) laryngoscope (39%) and Macintosh laryngoscope (42%). Glottis view was best with Bullard(®) laryngoscope (Grade 1 in 100%) and worst with Macintosh laryngoscope (Grade 1 in 2%). Difficulty of technique was rated with a VAS score of 2 (Bullard(®) laryngoscope), 4.5 (Storz DCI(®) laryngoscope) and 6 (Airtraq(®) - and Macintosh laryngoscopes). CONCLUSIONS: Inexperienced anesthetists have higher success rates and shorter intubation times with optical-assisted laryngoscopes compared with conventional Macintosh laryngoscope. Gyrus Infant Bullard(®) laryngoscope significantly undertakes best success rate and shortest intubation time with mildest impact to maxillary dents and easiest technique. Our findings support the hypothesis that optical laryngoscopes can be used successfully by inexperienced anesthetists in simulated difficult pediatric airway conditions.