Publications by authors named "Ashham Mansur"

33 Publications

TIM-3 Genetic Variants Are Associated with Altered Clinical Outcome and Susceptibility to Gram-Positive Infections in Patients with Sepsis.

Int J Mol Sci 2020 Nov 6;21(21). Epub 2020 Nov 6.

Department of Anesthesiology, University Medical Center, Georg August University, D-37075 Goettingen, Germany.

: Previous studies have reported the fundamental role of immunoregulatory proteins in the clinical phenotype and outcome of sepsis. This study investigated two functional single nucleotide polymorphisms (SNPs) of T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), which has a negative stimulatory function in the T cell immune response. : Patients with sepsis ( = 712) were prospectively enrolled from three intensive care units (ICUs) at the University Medical Center Goettingen since 2012. All patients were genotyped for the TIM-3 SNPs rs1036199 and rs10515746. The primary outcome was 28-day mortality. Disease severity and microbiological findings were secondary endpoints. : Kaplan-Meier survival analysis demonstrated a significantly lower 28-day mortality for TIM-3 rs1036199 AA homozygous patients compared to C-allele carriers (18% vs. 27%, = 0.0099) and TIM-3 rs10515746 CC homozygous patients compared to A-allele carriers (18% vs. 26%, = 0.0202). The TIM-3 rs1036199 AA genotype and rs10515746 CC genotype remained significant predictors for 28-day mortality in the multivariate Cox regression analysis after adjustment for relevant confounders (adjusted hazard ratios: 0.67 and 0.70). Additionally, patients carrying the rs1036199 AA genotype presented more Gram-positive and infections, and rs10515746 CC homozygotes presented more infections. : The studied TIM-3 genetic variants are associated with altered 28-day mortality and susceptibility to Gram-positive infections in sepsis.
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http://dx.doi.org/10.3390/ijms21218318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7664272PMC
November 2020

Favorable 90-Day Mortality in Obese Caucasian Patients with Septic Shock According to the Sepsis-3 Definition.

J Clin Med 2019 Dec 24;9(1). Epub 2019 Dec 24.

Department of Anesthesiology, University Medical Center, Georg August University, D-37075 Goettingen, Germany.

Septic shock is a frequent life-threatening condition and a leading cause of mortality in intensive care units (ICUs). Previous investigations have reported a potentially protective effect of obesity in septic shock patients. However, prior results have been inconsistent, focused on short-term in-hospital mortality and inadequately adjusted for confounders, and they have rarely applied the currently valid Sepsis-3 definition criteria for septic shock. This investigation examined the effect of obesity on 90-day mortality in patients with septic shock selected from a prospectively enrolled cohort of septic patients. A total of 352 patients who met the Sepsis-3 criteria for septic shock were enrolled in this study. Body-mass index (BMI) was used to divide the cohort into 24% obese (BMI ≥ 30 kg/m) and 76% non-obese (BMI < 30 kg/m) patients. Kaplan-Meier survival analysis revealed a significantly lower 90-day mortality (31% vs. 43%; = 0.0436) in obese patients compared to non-obese patients. Additional analyses of baseline characteristics, disease severity, and microbiological findings outlined further statistically significant differences among the groups. Multivariate Cox regression analysis estimated a significant protective effect of obesity on 90-day mortality after adjustment for confounders. An understanding of the underlying physiologic mechanisms may improve therapeutic strategies and patient prognosis.
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http://dx.doi.org/10.3390/jcm9010046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019854PMC
December 2019

Results of concomitant groin-free percutaneous temporary RVAD support using a centrifugal pump with a double-lumen jugular venous cannula in LVAD patients.

J Thorac Dis 2019 Apr;11(Suppl 6):S913-S920

Department of Cardiac Surgery, University Hospital of Heidelberg, Heidelberg, Germany.

Background: Modern left ventricular assist devices (LVAD) have evolved to become standard of care in severe heart failure (HF) patients. Right HF (RHF) is a major complication responsible for early mortality. Several techniques for temporary right ventricular assist device (t-RVAD) have been described before, baring relevant disadvantages such as limited mobilization or the need for re-thoracotomy. We describe the results of an alternative technique for t-RVAD using the Tandem Heart™ with ProtekDuo™ cannula.

Methods: An institutional retrospective single centre outcome analysis was performed including all permanent LVAD recipients with concomitant groin-free t-RVAD support.

Results: Between October 2015 and September 2017, 11 patients (10 male, 90.9%) were included. Preoperative NYHA class was 3.8±0.75 and INTERMACS class 3.5±1.5. Four (36.4%) patients were already on mechanical circulatory support (MCS) at time of implantation with 4 (36.4%) patients already on inotropic support. All LVAD implantations were performed on-pump and 3 cases (27.3%) were re-do cases. Mean t-RVAD duration was 16.8±9.5 days. Ten patients (90.9%) could be weaned from temporary RVAD support, 1 patient deceased on support. Mean ICU stay was 23.8±16.5 days, while 30-day survival was 72.7%. Follow-up was complete with 214.7±283 days. Three patients (27.3%) died following multi-organ failure (MOF), 1 patient (9.1%) following intracranial bleed 12 days after t-RVAD explantation. No severe t-RVAD associated complications were observed.

Conclusions: Our technique allows for safe groin-free t-RVAD providing all advantages of percutaneous implantation including complete mobilization and bedside explantation without any need for operation.
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http://dx.doi.org/10.21037/jtd.2018.11.121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6535488PMC
April 2019

Subparaneural Injection in Popliteal Sciatic Nerve Blocks Evaluated by MRI.

Open Med (Wars) 2019 24;14:346-353. Epub 2019 Apr 24.

Department of Anesthesiology, Emergency and Intensive Care Medicine, University Medical Center Goettingen, Robert-Koch Str. 40, 37075 Goettingen, Germany.

Intraneural injection of a local anesthetic can damage the nerve, yet it occurs frequently during distal sciatic block with no neurological sequelae. This has led to a controversy about the optimal needle tip placement that results from the particular anatomy of the sciatic nerve with its paraneural sheath. The study population included patients undergoing lower extremity surgery under popliteal sciatic nerve block. Ultrasound-guidance was used to position the needle tip subparaneurally and to monitor the injection of the local anesthetic. Sonography and magnetic resonance imaging were used to assess the extent of the subparaneural injection. Twenty-two patients participated. The median sciatic cross-sectional area increased from 57.8 mm2 pre-block to 110.8 mm immediately post-block. An intraneural injection according to the current definition was seen in 21 patients. Two patients had sonographic evidence of an intrafascicular injection, which was confirmed by MRI in one patient (the other patient refused further examinations). No patient reported any neurological symptoms. A subparaneural injection in the popliteal segment of the distal sciatic nerve is actually rarely intraneural, i.e. intrafascicular. This may explain the discrepancy between the conventional sonographic evidence of an intraneural injection and the lack of neurological sequelae.
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http://dx.doi.org/10.1515/med-2019-0034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6534099PMC
April 2019

Lack of an Association between the Functional Polymorphism TREM-1 rs2234237 and the Clinical Course of Sepsis among Critically Ill Caucasian Patients-A Monocentric Prospective Genetic Association Study.

J Clin Med 2019 Mar 3;8(3). Epub 2019 Mar 3.

Department of Anesthesiology, University Medical Center, Georg August University, D-37075 Goettingen, Germany.

Sepsis is a life-threatening condition and a significant challenge for those working in intensive care, where it remains one of the leading causes of mortality. According to the sepsis-3 definition, sepsis is characterized by dysregulation of the host response to infection. The TREM-1 gene codes for the triggering receptor expressed on myeloid cells 1, which is part of the pro-inflammatory response of the immune system. This study aimed to determine whether the functional TREM-1 rs2234237 single nucleotide polymorphism was associated with mortality in a cohort of 649 Caucasian patients with sepsis. The 90-day mortality rate was the primary outcome, and disease severity and microbiological findings were analyzed as secondary endpoints. TREM-1 rs2234237 TT homozygous patients were compared to A-allele carriers for this purpose. Kaplan⁻Meier survival analysis revealed no association between the clinically relevant TREM-1 rs2234237 single nucleotide polymorphism and the 90-day or 28-day survival rate in this group of septic patients. In addition, the performed analyses of disease severity and the microbiological findings did not show significant differences between the TREM-1 rs2234237 genotypes. The TREM-1 rs2234237 genotype was not significantly associated with sepsis mortality and sepsis disease severity. Therefore, it was not a valuable prognostic marker for the survival of septic patients in the studied cohort.
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http://dx.doi.org/10.3390/jcm8030301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6463065PMC
March 2019

CTLA-4 Genetic Variants Predict Survival in Patients with Sepsis.

J Clin Med 2019 Jan 10;8(1). Epub 2019 Jan 10.

Department of Anesthesiology, University Medical Center, Georg August University, D-37075 Goettingen, Germany.

Cytotoxic T lymphocyte-associated protein 4 (CTLA-4) is a coinhibitory checkpoint protein expressed on the surface of T cells. A recent study by our working group revealed that the rs231775 single nucleotide polymorphism (SNP) in the CTLA-4 gene was associated with the survival of patients with sepsis and served as an independent prognostic variable. To further investigate the impact of CTLA-4 genetic variants on sepsis survival, we examined the effect of two functional SNPs, CTLA-4 rs733618 and CTLA-4 rs3087243, and inferred haplotypes, on the survival of 644 prospectively enrolled septic patients. Kaplan⁻Meier survival analysis revealed significantly lower 90-day mortality for rs3087243 G allele carriers ( = 502) than for AA-homozygous ( = 142) patients (27.3% vs. 40.8%, = 0.0024). Likewise, lower 90-day mortality was observed for TAA haplotype-negative patients ( = 197; compound rs733618 T/rs231775 A/rs3087243 A) than for patients carrying the TAA haplotype ( = 447; 24.4% vs. 32.9%, = 0.0265). Carrying the rs3087243 G allele hazard ratio (HR): 0.667; 95% confidence interval (CI): 0.489⁻0.909; = 0.0103) or not carrying the TAA haplotype (HR: 0.685; 95% CI: 0.491⁻0.956; = 0.0262) remained significant covariates for 90-day survival in the multivariate Cox regression analysis and thus served as independent prognostic variables. In conclusion, our findings underscore the significance of CTLA-4 genetic variants as predictors of survival of patients with sepsis.
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http://dx.doi.org/10.3390/jcm8010070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6352177PMC
January 2019

Anaemia requiring red blood cell transfusion is associated with unfavourable 90-day survival in surgical patients with sepsis.

BMC Res Notes 2018 Dec 11;11(1):879. Epub 2018 Dec 11.

Department of Anesthesiology, University Medical Center, Georg August University, Goettingen, Germany.

Objective: The mortality associated with sepsis remains unacceptably high, despite modern high-quality intensive care. Based on the results from previous studies, anaemia and its management in patients with sepsis appear to impact outcomes; however, the transfusion policy is still being debated, and the ideal approach may be extremely specific to the individual. This study aimed to investigate the long-term impact of anaemia requiring red blood cell (RBC) transfusion on mortality and disease severity in patients with sepsis. We studied a general surgical intensive care unit (ICU) population, excluding cardiac surgery patients. 435 patients were enrolled in this observational study between 2012 and 2016.

Results: Patients who received RBC transfusion between 28 days before and 28 days after the development of sepsis (n = 302) exhibited a significantly higher 90-day mortality rate (34.1% vs 19.6%; P = 0.004, Kaplan-Meier analysis). This association remained significant after adjusting for confounders in the multivariate Cox regression analysis (hazard ratio 1.68; 95% confidence interval 1.03-2.73; P = 0.035). Patients who received transfusions also showed significantly higher morbidity scores, such as SOFA scores, and ICU lengths of stay compared to patients without transfusions (n = 133). Our results indicate that anaemia and RBC transfusion are associated with unfavourable outcomes in patients with sepsis.
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http://dx.doi.org/10.1186/s13104-018-3988-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6290543PMC
December 2018

Paths of femoral nerve catheters placed using ultrasound-guided in plane vs out of plane techniques: A randomized controlled clinical trial.

Medicine (Baltimore) 2018 Oct;97(43):e12958

Department of Anesthesiology, Emergency and Intensive Care Medicine, University Medical Center, University of Goettingen, Goettingen.

Background: Continuous blockade of the femoral nerve is widely used for postoperative analgesia after hip surgery. It can be achieved by ultrasound-guided placement of a femoral nerve catheter via either the in plane (IP) or out of plane (OOP) technique. On the basis of postoperative radiographs, we evaluated the paths of femoral nerve catheters with respect to both techniques and its effect on postoperative analgesia.

Methods: Thirty-four patients were randomized to receive a radiopaque femoral nerve catheter via either the IP or OOP technique. The paths and tip position of the catheters were evaluated in postoperative frontal radiographs of the operated hip joint concerning a predefined target region and four neighboring regions. Pain scores were assessed using a numeric rating scale (0-10).

Results: Sixteen IP patients and 18 OOP patients were included in the study. The catheter path was radiographically evaluated in 13 IP patients and in 10 OOP patients. The catheter tips were located within the target region in 39% of the IP group and in 50% of the OOP group. The catheter tip was 0.00 cm [-3.80 to 3.84] and -1.19 cm [-12.27 to 0.00] (median [range]) from the target region in the OOP group and IP group, respectively (P = .045). Catheters flipped distally more often in the IP group (IP: 61.5%, OOP: 10.0%; P = .01). There were no marked differences in the pain scores of either group.

Conclusion: Femoral nerve catheters inserted by the ultrasound-guided IP technique flip distally more frequently than catheters inserted by the OOP technique. Moreover, the distance between the catheter tip and the trunk of the femoral nerve is greater for IP catheters than for OOP catheters. Despite these findings, postoperative analgesia did not seem to differ between the 2 techniques.
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http://dx.doi.org/10.1097/MD.0000000000012958DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6221616PMC
October 2018

The CTLA-4 rs231775 GG genotype is associated with favorable 90-day survival in Caucasian patients with sepsis.

Sci Rep 2018 10 11;8(1):15140. Epub 2018 Oct 11.

Department of Anesthesiology, University Medical Center, Georg August University, Robert-Koch-Str. 40, D-37075, Goettingen, Germany.

Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is a surface protein on T cells, that has an inhibitory effect on the host immune reaction and prevents overreaction of the immune system. Because the functional single-nucleotide polymorphism (SNP) rs231775 of the CTLA-4 gene is associated with autoimmune diseases and because of the critical role of the immune reaction in sepsis, we intended to examine the effect of this polymorphism on survival in patients with sepsis. 644 septic adult Caucasian patients were prospectively enrolled in this study. Patients were followed up for 90 days. Mortality risk within this period was defined as primary outcome parameter. Kaplan-Meier survival analysis revealed a significantly lower 90-day mortality risk among GG homozygous patients (n = 101) than among A allele carriers (n = 543; 22% and 32%, respectively; p = 0.03565). Furthermore, the CTLA-4 rs231775 GG genotype remained a significant covariate for 90-day mortality risk after controlling for confounders in the multivariate Cox regression analysis (hazard ratio: 0.624; 95% CI: 0.399-0.975; p = 0.03858). In conclusion, our study provides the first evidence for CTLA-4 rs231775 as a prognostic variable for the survival of patients with sepsis and emphasizes the need for further research to reveal potential functional associations between CTLA-4 and the immune pathophysiology of sepsis.
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http://dx.doi.org/10.1038/s41598-018-33246-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6181961PMC
October 2018

Prehospital ultrasound-guided nerve blocks improve reduction-feasibility of dislocated extremity injuries compared to systemic analgesia. A randomized controlled trial.

PLoS One 2018 2;13(7):e0199776. Epub 2018 Jul 2.

Department of Anesthesiology, Emergency and Intensive Care Medicine, University Medical Center, University of Goettingen, Goettingen, Germany.

Background: Out-of-hospital analgosedation in trauma patients is challenging for emergency physicians due to associated complications. We compared peripheral nerve block (PNB) with analgosedation (AS) as an analgetic approach for patients with isolated extremity injury, assuming that prehospital required medical interventions (e.g. reduction, splinting of dislocation injury) using PNB are less painful and more feasible compared to AS.

Methods: Thirty patients (aged 18 or older) were randomized to receive either ultrasound-guided PNB (10 mL prilocaine 1%, 10 mL ropivacaine 0.2%) or analgosedation (midazolam combined with s-ketamine or with fentanyl). Reduction-feasibility was classified (easy, intermediate, impossible) and pain scores were assessed using numeric rating scales (NRS 0-10).

Results: Eighteen patients were included in the PNB-group and twelve in the AS-group; 15 and 9 patients, respectively, suffered dislocation injury. In the PNB-group, reduction was more feasible (easy: 80.0%, impossible: 20.0%) compared to the AS-group (easy: 22.2%, intermediate: 22.2%, impossible: 55.6%; p = 0.01). During medical interventions, 5.6% [1/18] of the PNB-patients and 58.3% [7/12] of the AS-patients experienced pain (p<0.01). Recorded pain scores were significantly lower in the PNB-group during prehospital medical intervention (median[IQR] NRS PNB: 0[0-0]) compared to the AS-group (6[0-8]; p<0.001) as well as on first day post presentation (NRS PNB: 1[0-5], AS: 5[5-7]; p = 0.050). All patients of the PNB-group would recommend their analgesic technique (AS: 50.0%, p<0.01).

Conclusions: Prehospital ultrasound-guided PNB is rapidly performed in extremity injuries with high success. Compared to the commonly used AS in trauma patients, PNB significantly reduces pain intensity and severity.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0199776PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6028078PMC
January 2019

Prognostic relevance of hemodialysis for short-term survival in patients after LVAD implantation.

Sci Rep 2018 06 4;8(1):8546. Epub 2018 Jun 4.

Department of Cardiac Surgery, University Hospital of Heidelberg, Heidelberg, Germany.

End-stage heart failure (HF) is associated with renal failure (RF). This study aimed to determine the prognostic influence of RF and post-operative hemodialysis on short-term survival following left ventricular assist device (LVAD) implantation. This retrospective study includes 68 patients undergoing LVAD treatment. Kidney function was recorded prior to LVAD implantation, immediately afterwards and after 30 days, noting the need for hemodialysis. Median pre-operative Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) classification was 3.47 ± 1.08. 30 days after implantation there was a significant improvement of estimated glomerular filtration rate (eGFR) and reduction of blood urea nitrogen (BUN). Of pre-operative RF parameters, BUN was associated with increased mortality and need for early post-operative hemodialysis. Post-operative hemodialysis was associated with significantly lower short-term survival, while pre-operative hemodialysis did not impact mortality. Post-operative acute kidney injury (AKI) requiring hemodialysis can be regarded as a strong negative prognostic marker for short-term survival. The absence of a clear correlation between most routine RF parameters and survival or the need for early post-operative hemodialysis calls into question the predictive value of pre-operative RF. The negative association of only post-operative hemodialysis on short-term survival emphasises the impact of the occurrence of AKI.
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http://dx.doi.org/10.1038/s41598-018-26515-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5986780PMC
June 2018

Prognostic relevance of hemodialysis for short-term survival in patients after LVAD implantation.

Sci Rep 2018 06 4;8(1):8546. Epub 2018 Jun 4.

Department of Cardiac Surgery, University Hospital of Heidelberg, Heidelberg, Germany.

End-stage heart failure (HF) is associated with renal failure (RF). This study aimed to determine the prognostic influence of RF and post-operative hemodialysis on short-term survival following left ventricular assist device (LVAD) implantation. This retrospective study includes 68 patients undergoing LVAD treatment. Kidney function was recorded prior to LVAD implantation, immediately afterwards and after 30 days, noting the need for hemodialysis. Median pre-operative Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) classification was 3.47 ± 1.08. 30 days after implantation there was a significant improvement of estimated glomerular filtration rate (eGFR) and reduction of blood urea nitrogen (BUN). Of pre-operative RF parameters, BUN was associated with increased mortality and need for early post-operative hemodialysis. Post-operative hemodialysis was associated with significantly lower short-term survival, while pre-operative hemodialysis did not impact mortality. Post-operative acute kidney injury (AKI) requiring hemodialysis can be regarded as a strong negative prognostic marker for short-term survival. The absence of a clear correlation between most routine RF parameters and survival or the need for early post-operative hemodialysis calls into question the predictive value of pre-operative RF. The negative association of only post-operative hemodialysis on short-term survival emphasises the impact of the occurrence of AKI.
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http://dx.doi.org/10.1038/s41598-018-26515-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5986780PMC
June 2018

Severe bilateral isolated coronary ostial lesions as a rare manifestation of radiation-induced cardiac disease A case report.

Medicine (Baltimore) 2018 Mar;97(13):e9867

Department of Cardiothoracic Surgery, Harefield Hospital, Harefield, UK Department of Cardiac Surgery, University Hospital Oldenburg, Oldenburg Department of Anesthesiology, University Medical Centre, Georg August University, Goettingen Department of Cardiac Surgery, University Hospital Frankfurt, Frankfurt, Germany.

Rationale: With advances in contemporary radiotherapy techniques, and as cancer survival improves, severe isolated coronary ostial disease may develop many years following mediastinal radiotherapy, even in the absence of classical cardiovascular risk factors.

Patient Concerns: We describe the case of a 73-year-old woman with previous chest radiotherapy for breast cancer who underwent coronary artery bypass graft surgery for severe bilateral coronary ostial lesions.

Diagnoses: Coronary angiography demonstrated severe, isolated bilateral coronary ostial lesions.

Interventions: The patient underwent urgent coronary artery bypass graft surgery to treat her critical coronary artery disease.

Outcomes: Intra-operatively, internal mammary arteries were not amenable to harvesting due to very dense mediastinal adhesions. Therefore, saphenous vein grafts were performed to the left anterior descending, distal left circumflex, obtuse marginal and distal right coronary arteries. The patient made a satisfactory in-hospital recovery, and was subsequently discharged back to her local hospital for rehabilitation.

Lessons: Patients successfully treated with mediastinal radiotherapy require careful long-term follow-up for the assessment of radiation-induced coronary artery disease. Importantly, mediastinal irradiation may preclude internal mammary artery utilization, and thus alter the strategy for surgical myocardial revascularization.
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http://dx.doi.org/10.1097/MD.0000000000009867DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5895407PMC
March 2018

Pre-hospital transthoracic echocardiography for early identification of non-ST-elevation myocardial infarction in patients with acute coronary syndrome.

Crit Care 2018 02 7;22(1):29. Epub 2018 Feb 7.

Department of Anesthesiology, Emergency and Intensive Care Medicine, University Medical Center, University of Goettingen, Robert-Koch Str. 40, 37075, Göttingen, Germany.

Background: Non-ST elevation myocardial infarction (NSTEMI) is a common manifestation of acute coronary syndrome (ACS), but delayed diagnosis can increase mortality. In this proof of principle study, the emergency physician performed transthoracic echocardiography (TTE) on scene to determine whether NSTEMI could be correctly diagnosed pre-hospitalization. This could expedite admission to the appropriate facility and reduce the delay until initiation of correct therapy.

Methods: Pre-hospital TTE was performed on scene by the emergency physician in patients presenting with ACS but without ST-elevation in the initial 12-lead electrocardiography (ECG) (NSTE-ACS). A presumptive NSTEMI diagnosis was made if regional wall motion abnormalities (RWMA) were detected. These patients were admitted directly to a specialist cardiac facility. Patient characteristics and pre-admission and post-admission clinical, pre-hospital TTE data, and therapeutic measures were recorded.

Results: Patients with NSTE-ACS (n = 53; 72.5 ± 13.4 years of age; 23 female) were studied. The 20 patients with pre-hospital RWMA and presumptive NSTEMI, and two without RWMA were conclusively diagnosed with NSTEMI in hospital. Percutaneous coronary intervention was performed in 50% of the patients presumed to have NSTEMI immediately after admission. The RWMA seen before hospital TTE corresponded with the in-hospital ECG findings and/or the supply regions of the occluded coronary vessels seen during PCI in 85% of the cases. The diagnostic sensitivity of pre-hospital TTE for NSTEMI was 90.9% with 100% specificity.

Conclusions: Pre-hospital transthoracic echocardiography by the emergency physician can correctly diagnose NSTEMI in more than 90% of cases. This can expedite the initiation of appropriate therapy and could thereby conceivably reduce morbidity and mortality.

Trial Registration: Deutsche Register klinischer Studien, DRKS00004919 . Registered on 29 April 2013.
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http://dx.doi.org/10.1186/s13054-017-1929-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5802056PMC
February 2018

Use of taurolidine in lung transplantation for cystic fibrosis and impact on bacterial colonization.

Eur J Cardiothorac Surg 2018 03;53(3):603-609

Department of Cardiothoracic Transplantation and Mechanical Circulatory Support, Royal Brompton & Harefield NHS Foundation Trust, Harefield Hospital, London, UK.

Objectives: The presence of bacterial colonization that causes chronic pulmonary infections in cystic fibrosis (CF) patients remains a key issue before lung transplantation. We sought to assess the impact of intraoperative taurolidine lavage on bacterial colonization and long-term outcomes following lung transplantation in CF patients.

Methods: Between 2007 and 2013, 114 CF patients underwent lung transplantation at our institute, and taurolidine 2% bronchial lavage was applied in a substantial proportion of patients (n = 42). A detailed analysis of donor and recipient bacterial colonization status in treatment and control groups and their impact on outcome was performed.

Results: The proportion of recipients colonized with Pseudomonas aeruginosa was lower in the taurolidine group at 3 months (P < 0.001) and at 1 year (P = 0.053) postoperatively, despite no differences before transplant (P = 1.000). Moreover, a complete eradication of Burkholderia cepacia and Stenotrophomonas maltophilias colonizations could be achieved in the taurolidine group, whereas in the non-taurolidine group, persistent B. cepacia and S. maltophilias colonizations were observed. Early outcome in the taurolidine group was superior regarding fraction of expired volume in 1 s at 3 and 6 months after surgery with 74.5 ± 14.6 vs 60.4 ± 17.5 (P < 0.001) and 80.6 ± 16.9 vs 67.2 ± 19.4 (P = 0.005) percent of predicted values, respectively. In terms of long-term overall survival (P = 0.277) and freedom from bronchiolitis obliterans syndrome (P = 0.979), both groups were comparable.

Conclusions: Taurolidine might be associated with a reduced proportion of CF patients colonized with multiresistant pathogens, particularly with P. aeruginosa. Long-term results should be further assessed in larger multicentre trials.
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http://dx.doi.org/10.1093/ejcts/ezx359DOI Listing
March 2018

Extracorporeal life support with left ventricular decompression-improved survival in severe cardiogenic shock: results from a retrospective study.

PeerJ 2017 29;5:e3813. Epub 2017 Sep 29.

Department of Cardiac Surgery, University Hospital Heidelberg, Heidelberg, Germany.

Objective: Extracorporeal life support (ECLS) is a life-saving procedure used in the treatment of severe cardiogenic shock. Within this retrospective single centre study, we examined our experience in this critically ill patient cohort to assess outcomes and clinical parameters by comparison of ECLS with or without selective left ventricular decompression.

Methods: Between 2004 and 2014 we evaluated 48 adult patients with INTERMACS level 1 heart failure (age 49.7 ± 19.5 years), who received either central ECLS with ( = 20, 41.7%) or ECLS without ( = 28, 58.3%, including 10 peripheral ECLS) integrated left ventricular vent in our retrospective single centre trial.

Results: Follow up was 100% with a mean of 0.83 ± 1.85 years. Bridge to ventricular assist device was feasible in 29.2% ( = 14), bridge to transplant in 10.4% ( = 5) and bridge to recovery in 8.3% ( = 4). Overall 30-day survival was 37.5%, 6-month survival 27.1% and 1-year survival 25.0%. ECLS support with left ventricular decompression showed favourable 30-day survival compared to ECLS without left ventricular decompression ( = 0.034). Thirty-day as well as long-term survival did not differ between the subgroups (central ECLS with vent, ECLS without vent and peripheral ECLS without vent). Multivariate logistic regression adjusted for age and gender revealed ECLS without vent as independent factor influencing 30-day survival.

Conclusion: ECLS is an established therapy for patients in severe cardiogenic shock. Independent of the ECLS approach, 30-day mortality is still high but with superior 30-day survival for patients with ECLS and left ventricular venting. Moreover, by unloading the ventricle, left ventricular decompression may provide an important time window for recovery or further treatment, such as bridge to bridge or bridge to transplant.
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http://dx.doi.org/10.7717/peerj.3813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5624302PMC
September 2017

The FER rs4957796 TT genotype is associated with unfavorable 90-day survival in Caucasian patients with severe ARDS due to pneumonia.

Sci Rep 2017 08 29;7(1):9887. Epub 2017 Aug 29.

Department of Anaesthesiology, University Medical Centre, Georg August University, Robert-Koch-Str.40, D-37075, Goettingen, Germany.

A recent genome-wide association study showed that a genetic variant within the FER gene is associated with survival in patients with sepsis due to pneumonia. Because severe pneumonia is the main cause of acute respiratory distress syndrome (ARDS), we aimed to investigate the effect of the FER polymorphism rs4957796 on the 90-day survival in patients with ARDS due to pneumonia. An assessment of a prospectively collected cohort of 441 patients with ARDS admitted to three intensive care units at the University Medical Centre identified 274 patients with ARDS due to pneumonia. The 90-day mortality risk was recorded as the primary outcome parameter. Sepsis-related organ failure assessment (SOFA) scores and organ support-free days were used as the secondary variables. FER rs4957796 TT-homozygous patients were compared with C-allele carriers. The survival analysis revealed a higher 90-day mortality risk among T homozygotes than among C-allele carriers (p = 0.0144) exclusively in patients with severe ARDS due to pneumonia. The FER rs4957796 TT genotype remained a significant covariate for the 90-day mortality risk in the multivariate analysis (hazard ratio, 4.62; 95% CI, 1.58-13.50; p = 0.0050). In conclusion, FER rs4957796 might act as a prognostic variable for survival in patients with severe ARDS due to pneumonia.
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http://dx.doi.org/10.1038/s41598-017-08540-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5575093PMC
August 2017

Combination of general anesthesia and peripheral nerve block with low-dose ropivacaine reduces postoperative pain for several days after outpatient arthroscopy: A randomized controlled clinical trial.

Medicine (Baltimore) 2017 Feb;96(6):e6046

Department of Anesthesiology, Emergency and Intensive Care Medicine, University Medical Center, University of Göttingen, Göttingen, Germany.

Background: Effective methods for postoperative pain relief are an important concern in outpatient surgery. For arthroscopies we combine a single-shot peripheral nerve block using low-volume, low-concentration ropivacaine with general anesthesia. We hypothesized that the patients would have less postoperative pain and be more rapidly home ready than after general anesthesia alone.

Methods: Patients (American Society of Anesthesiologists I-III, 18-80 years old) scheduled for outpatient arthroscopy on the upper or lower extremity were randomized to have either a combination of peripheral nerve block and general anesthesia (NB + GA, study group) or general anesthesia alone (GA, control group). The relevant nerve was localized by ultrasound and 10 mL ropivacaine 0.2% was injected. General anesthesia was with propofol and remifentanil. Numeric rating scales were used to assess pain and patient satisfaction in the recovery room, on the evening of surgery, and on the following 2 days.

Results: A total of 120 patients participated in the study (NB + GA: 61; GA: 59). The percentage of patients reporting relevant pain in the recovery room were 0% versus 44% (P < 0.001), on the evening after surgery 3% versus 80% (P < 0.001), and on days 1 and 2 postsurgery 12% versus 73% and 12% versus 64% (NB + GA vs GA, respectively). Median time to home discharge was NB + GA 34.5 min (range 15-90) versus GA 55 min (20-115) (P < 0.001).

Conclusions: The combination of a peripheral nerve block with low-dose ropivacaine and general anesthesia reduced postoperative pain compared with general anesthesia alone for several days after outpatient arthroscopy. It also shortened the time to home discharge.
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http://dx.doi.org/10.1097/MD.0000000000006046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5313006PMC
February 2017

Influence of isoflurane on the diastolic pressure-flow relationship and critical occlusion pressure during arterial CABG surgery: a randomized controlled trial.

PeerJ 2016 26;4:e1619. Epub 2016 Jan 26.

Department of Anesthesiology, University Medical Center Goettingen , Goettingen , Germany.

The effects of isoflurane on the determinants of blood flow during Coronary Artery Bypass Graft (CABG) surgery are not completely understood. This study characterized the influence of isoflurane on the diastolic Pressure-Flow (P-F) relationship and Critical Occlusion Pressure (COP) during CABG surgery. Twenty patients undergoing CABG surgery were studied. Patients were assigned to an isoflurane or control group. Hemodynamic and flow measurements during CABG surgery were performed twice (15 minutes after the discontinuation of extracorporeal circulation (T15) and again 15 minutes later (T30)). The zero flow pressure intercept (a measure of COP) was extrapolated from a linear regression analysis of the instantaneous diastolic P-F relationship. In the isoflurane group, the application of isoflurane significantly increased the slope of the diastolic P-F relationship by 215% indicating a mean reduction of Coronary Vascular Resistance (CVR) by 46%. Simultaneously, the Mean Diastolic Aortic Pressure (MDAP) decreased by 19% mainly due to a decrease in the systemic vascular resistance index by 21%. The COP, cardiac index, heart rate, Left Ventricular End-Diastolic Pressure (LVEDP) and Coronary Sinus Pressure (CSP) did not change significantly. In the control group, the parameters remained unchanged. In both groups, COP significantly exceeded the CSP and LVEDP at both time points. We conclude that short-term application of isoflurane at a sedative concentration markedly increases the slope of the instantaneous diastolic P-F relationship during CABG surgery implying a distinct decrease with CVR in patients undergoing CABG surgery.
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http://dx.doi.org/10.7717/peerj.1619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4783760PMC
March 2016

Pre-Existing Chronic Pain Influences the Severity of Acute Herpes Zoster Pain-A Prospective Observational Cohort Study.

Pain Med 2016 Jul;17(7):1317-1328

*Department of Anaesthesiology, Pain Clinic.

Objective: Pre-existing chronic pain has been associated with severe postoperative pain. To analyze the impact of chronic pain on non-surgical acute pain, a cohort of patients with acute herpes zoster was studied.

Methods: Consecutive patients, who needed hospitalization because of an acute zoster infection, were characterized and compared according to their pain history. Pain intensity, pain-related function, analgesic consumption, and psychological and physiological characteristics were assessed as baseline parameters on the day of hospitalization. Pain intensity and functional restrictions were evaluated on day 1, 4, 7, and on the day of discharge. The analgesic consumption was recorded and scored for each of these days. A multivariate analysis was performed for individual predictors.

Results: 59 patients were included; 25 patients (42.4%) had pre-existing chronic pain. These patients had more severe acute zoster pain on all assessment days and were more restricted in function, such as sleep quality and mobilization. There were, however, no differences in analgesic consumption. In patients without chronic pain, only the amount of analgesic consumption was associated with the severity of zoster pain. In contrast, in patients with chronic pain, the severity of the chronic pain, physical health, and the extent of neuropathic pain characteristics were associated with the intensity of zoster-related acute pain, while analgesic consumption was not.

Conclusions: Patients with chronic pain had higher intensity of zoster-related acute pain. Furthermore, they showed more pain-related dysfunction and needed longer hospitalization than patients without chronic pain. These results go along with findings for acute postoperative pain.
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http://dx.doi.org/10.1093/pm/pnv116DOI Listing
July 2016

Extended Recipient Criteria in Lung Transplantation: Impact of Pleural Abnormalities on Primary Graft Dysfunction.

Ann Thorac Surg 2016 Jun 23;101(6):2112-9. Epub 2016 Feb 23.

Department of Cardiothoracic Transplantation and Mechanical Circulatory Support, Royal Brompton & Harefield NHS Foundation Trust, Harefield Hospital, Hill End Road, Harefield, Middlesex, United Kingdom.

Background: Because of improved surgical expertise and intraoperative management, pleural disease (PD+) represents a relatively minor contraindication to lung transplantation (LTx). The presence of pleural abnormalities from previous procedures or pleural involvement from fungal or bacterial disease is not considered a limiting factor for LTx. However there are no studies available to assess the impact of pleural diseases on short- and midterm outcomes after LTx.

Methods: We retrospectively reviewed 163 consecutive patients who underwent LTx between 2010 and 2013. Patients were divided according to the presence of pleural abnormalities before the operation (PD+ versus PD-). The primary end point of the study was primary graft dysfunction (PGD; grade 3) and overall survival. To avoid possible selection bias and to heck the robustness of the results, a propensity score-matching analysis (1:3) was performed.

Results: A total of 26 patients (16%) had pleural abnormalities before transplantation. Intra- and postoperative variables were comparable. PD+ was associated with a significantly higher incidence of PGD at 0 and 48 hours postoperatively (p = 0.037 and p = 0.032, respectively). Moreover, PD+ was associated with significantly worse survival at 3 months (p = 0.021). Although there was a trend toward worse early overall survival in the Kaplan-Meier estimate (Breslow p = 0.050), midterm survival was comparable (log-rank p = 0.240).

Conclusions: LTx in patients with preoperative pleural abnormalities is feasible. Identifying higher-risk recipients with pleural abnormalities might have important clinical relevance because of a higher incidence of PGD and worse early survival, even though midterm survival is comparable.
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http://dx.doi.org/10.1016/j.athoracsur.2015.11.068DOI Listing
June 2016

Perioperative Blood Glucose Levels <150 mg/dL are Associated With Improved 5-Year Survival in Patients Undergoing On-Pump Cardiac Surgery: A Prospective, Observational Cohort Study.

Medicine (Baltimore) 2015 Nov;94(45):e2035

From the Department of Anesthesiology, University Medical Center, Georg August University, Goettingen, Germany (AM, IB, IFB, MB, JH); Department of Cardiothoracic Transplantation and Mechanical Support, Royal Brompton and Harefield Hospital, Harefield, London, UK (AFP); Department of Medical Informatics, University of Amsterdam, Amsterdam, The Netherlands (AAH); and Department of Medical Statistics, University Medical Center, Georg August University, Goettingen, Germany (TB).

Hyperglycemia is common during and after Coronary Artery Bypass Graft Surgery (CABGS) and has been shown to be associated with poor clinical outcomes. In this study, we hypothesized that a moderate perioperative mean blood glucose level of <150 mg/dL improves long-term survival in cardiac surgery patients. We conducted a prospective, observational cohort study in the heart center of the University Medical Center of Goettingen, Germany. Patients undergoing on-pump cardiac surgery were enrolled in this investigation. After evaluating perioperative blood glucose levels, patients were classified into 2 groups based on mean glucose levels: Glucose ≥150 mg/dL and Glucose <150 mg/dL. Patients were followed up for 5 years, and mortality within this period was recorded as the primary outcome parameter. Secondary outcome parameters included the length of ICU stay, the use of inotropic agents, the length of hospital stay, and the in-hospital mortality. A total of 455 consecutive patients who underwent cardiac surgery with cardiopulmonary bypass were enrolled in this investigation. A Kaplan-Meier survival analysis of the 5-year mortality risk revealed a higher mortality risk among patients with glucose levels ≥150 mg/dL (P = 0.0043, log-rank test). After adjustment for confounders in a multivariate Cox regression model, the association between glucose ≥150 mg/dL and 5-year mortality remained significant (hazard ratio, 2.10; 95% CI, 1.30-3.39; P = 0.0023). This association was corroborated by propensity score matching, in which Kaplan-Meier survival analysis demonstrated significant improvement in the 5-year survival of patients with glucose levels <150 mg/dL (P = 0.0339). Similarly, in-hospital mortality was significantly higher in patients with glucose ≥150 mg/dL compared with patients with glucose <150 mg/dL. Moreover, patients in the Glucose ≥150 mg/dL group required significantly higher doses of the inotropic agent Dobutamine (mg/d) compared with patients in the Glucose <150 mg/dL group (20.6 ± 62.3 and 10.5 ± 40.7, respectively; P = 0.0104). Moreover, patients in the Glucose ≥150 mg/dL group showed a significantly longer hospital stay compared with patients in the Glucose <150 mg/dL group (28 ± 23 and 24 ± 19, respectively; P = 0.0297). We conclude that perioperative blood glucose levels <150 mg/dL are associated with improved 5-year survival in patients undergoing cardiac surgery. More studies are warranted to explain this effect.
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http://dx.doi.org/10.1097/MD.0000000000002035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4912304PMC
November 2015

Genetic Polymorphisms in Endothelin-1 as Predictors for Long-Term Survival and the Cardiac Index in Patients Undergoing On-Pump Cardiac Surgery.

PLoS One 2015 29;10(6):e0131155. Epub 2015 Jun 29.

Department of Anesthesiology, University Medical Center, Georg August University, Robert-Koch-Str.40, D-37075 Goettingen, Germany.

Genetic variants within the endothelin-1 gene (EDN1) have been associated with several cardiovascular diseases and may act as genetic prognostic markers. Here, we explored the overall relevance of EDN1 polymorphisms for long-term survival in patients undergoing on-pump cardiac surgery. A prospectively collected cohort of 455 Caucasian patients who underwent cardiac surgery with cardiopulmonary bypass was followed up for 5 years. The obtained genotypes and inferred haplotypes were analyzed for their associations with the five-year mortality rate (primary endpoint). The EDN1 T-1370G and K198N genotype distributions did not deviate from Hardy-Weinberg equilibrium and the major allele frequencies were 83% and 77%, respectively. The cardiovascular risk factors were equally distributed in terms of the different genotypes and haplotypes associated with the two polymorphisms. The five-year mortality rate did not differ among the different EDN1 T-1370G and K198N genotypes and haplotypes. Haplotype analysis revealed that carriers of the G-T (compound EDN1 T-1370G G/K198N T) haplotype had a higher cardiac index than did non-carriers (p = 0.0008); however, this difference did not reach significance after adjusting for multiple testing. The results indicate that common variations in EDN1 do not act as prognostic markers for long-term survival in patients undergoing on-pump cardiac surgery.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0131155PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4487899PMC
April 2016

Impact of statin therapy on mortality in patients with sepsis-associated acute respiratory distress syndrome (ARDS) depends on ARDS severity: a prospective observational cohort study.

BMC Med 2015 Jun 1;13:128. Epub 2015 Jun 1.

Department of Anesthesiology, University Medical Center, Georg August University, D-37075, Goettingen, Germany.

Background: Previous investigations have presumed a potential therapeutic effect of statin therapy in patients with acute respiratory distress syndrome (ARDS). Statins are expected to attenuate inflammation in the lungs of patients with ARDS due to their anti-inflammatory effects. Clinical investigations of the role of statin therapy have revealed contradictory results. This study aimed to investigate whether pretreatment and continuous therapy with statins in patients with sepsis-associated ARDS are associated with 28-day survival according to disease severity (mild, moderate, or severe).

Methods: Patients with sepsis-associated ARDS from the surgical intensive care were enrolled in this prospective observational investigation. ARDS was classified into three groups (mild, moderate, and severe); 28-day mortality was recorded as the primary outcome variable and organ failure was recorded as secondary outcome variable. Sequential Organ Failure Assessment scores and the requirements for organ support were evaluated throughout the observational period to assess organ failure.

Results: 404 patients with sepsis-associated ARDS were enrolled in this investigation. The distribution of the ARDS subgroups was 13 %, 59 %, and 28 % for mild, moderate, and severe disease, respectively. Statin therapy improved 28-day survival exclusively in the patients with severe ARDS compared with patients without statin therapy (88.5 % and 62.5 %, respectively; P = 0.0193). To exclude the effects of several confounders, we performed multivariate Cox regression analysis, which showed that statin therapy remained a significant covariate for mortality (hazard ratio, 5.46; 95 % CI, 1.38-21.70; P = 0.0156). Moreover, after carrying a propensity score-matching in the severe ARDS cohort, Kaplan-Meier survival analysis confirmed the improved 28-day survival among patients with statin therapy (P = 0.0205). Patients with severe ARDS who received statin therapy had significantly more vasopressor-free days compared with those without statin therapy (13 ± 7 and 9 ± 7, respectively; P = 0.0034), and they also required less extracorporeal membrane oxygenation (ECMO) therapy and had more ECMO-free days (18 ± 9 and 15 ± 9, respectively; P = 0.0873).

Conclusions: This investigation suggests a beneficial effect of continuous statin therapy in patients with severe sepsis-associated ARDS and a history of prior statin therapy. Further study is warranted to elucidate this potential effect.
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http://dx.doi.org/10.1186/s12916-015-0368-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4462111PMC
June 2015

The CD14 rs2569190 TT Genotype Is Associated with an Improved 30-Day Survival in Patients with Sepsis: A Prospective Observational Cohort Study.

PLoS One 2015 28;10(5):e0127761. Epub 2015 May 28.

Department of Anesthesiology, University Medical Center, Georg August University, Goettingen, Germany.

According to previous investigations, CD14 is suggested to play a pivotal role in initiating and perpetuating the pro-inflammatory response during sepsis. A functional polymorphism within the CD14 gene, rs2569190, has been shown to impact the pro-inflammatory response upon stimulation with lipopolysaccharide, a central mediator of inflammation in sepsis. In this study, we hypothesized that the strong pro-inflammatory response induced by the TT genotype of CD14 rs2569190 may have a beneficial effect on survival (30-day) in patients with sepsis. A total of 417 adult patients with sepsis (and of western European descent) were enrolled into this observational study. Blood samples were collected for rs2569190 genotyping. Patients were followed over the course of their stay in the ICU, and the 30-day mortality risk was recorded as the primary outcome parameter. Sepsis-related organ failure assessment (SOFA) scores were quantified at sepsis onset and throughout the observational period to monitor organ failure as a secondary variable. Moreover, organ support-free days were evaluated as a secondary outcome parameter. TT-homozygous patients were compared to C-allele carriers. Kaplan-Meier survival analysis revealed a higher 30-day mortality risk among C-allele carriers compared with T homozygotes (p = 0.0261). To exclude the effect of potential confounders (age, gender, BMI and type of infection) and covariates that varied at baseline with a p-value < 0.2 (e.g., comorbidities), we performed multivariate Cox regression analysis to examine the survival time. The CD14 rs2569190 C allele remained a significant covariate for the 30-day mortality risk in the multivariate analysis (hazard ratio, 2.11; 95% CI, 1.08-4.12; p = 0.0282). The 30-day mortality rate among C allele carriers was 23%, whereas the T homozygotes had a mortality rate of 13%. Additionally, an analysis of organ-specific SOFA scores revealed a significantly higher SOFA-Central nervous system score among patients carrying the C allele compared with T-homozygous patients (1.9±1.1 and 1.6±1.0, respectively; p = 0.0311). In conclusion, CD14 rs2569190 may act as a prognostic variable for the short-term outcome (30-day survival) in patients with sepsis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0127761PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4447461PMC
April 2016

Ketamine in outpatient arthroscopic shoulder surgery: Effects on postoperative pain, hemodynamic stability and process times.

Open Med (Wars) 2015 28;10(1):297-305. Epub 2015 May 28.

Center for Anesthesiology, Emergency and Intensive Care Medicine, University Hospital Göttingen, Robert-Koch Str. 40, 37075 Göttingen, Germany, Tel.: +49 551 396051.

Background: Pain after arthroscopic shoulder surgery is often severe, and establishing a pain treatment regimen that does not delay discharge can be challenging. The reported ability of ketamine to prevent opioid-induced hyperalgesia has not been investigated in this particular setting.

Methods: 300 adult patients scheduled for shoulder arthroscopy under general anesthesia were recruited for this observational clinical trial and were allotted to either receive 1mg/kg IV bolus of ketamine before surgery (ketamine group, KG) or to a control group (CG) without ketamine. NRS pain scores were obtained on the operative day and on postoperative days 1 and 2 and compared between groups. Secondary variables were blood pressure, heart rate, process times, satisfaction with the anesthetic and unwanted effects.

Results: Pain severity did not differ significantly between the groups at any time. Propofol injection rate and cumulative dose were higher in the KG. Heart rates and blood pressures were similar. Time to emergence and time in PACU were longer and vomiting was more frequent in patients given ketamine.

Conclusion: Preoperative low-dose ketamine added to a general anesthetic does not reduce perioperative pain after outpatient shoulder arthroscopy. It increases procedural times and the incidence of PONV.
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http://dx.doi.org/10.1515/med-2015-0043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5152989PMC
May 2015

Chronic kidney disease is associated with a higher 90-day mortality than other chronic medical conditions in patients with sepsis.

Sci Rep 2015 May 21;5:10539. Epub 2015 May 21.

Department of Anesthesiology, University Medical Center, Georg August University, Robert-Koch-Str.40, D-37075 Goettingen, Germany.

According to previous studies, the clinical course of sepsis could be affected by preexisting medical conditions, which are very common among patients with sepsis. This observational study aimed at investigating whether common chronic medical conditions affect the 90-day mortality risk in adult Caucasian patients with sepsis. A total of 482 patients with sepsis were enrolled in this study. The ninety-day mortality was the primary outcome; organ failure was the secondary outcome. Sepsis-related organ failure assessment (SOFA) scores and the requirements for organ support were evaluated to assess organ failure. A multivariate Cox regression model for the association between the 90-day mortality risk and chronic preexisting medical conditions adjusted for all relevant confounders and mortality predictors revealed the highest hazard ratio for patients with chronic kidney disease (CKD) (hazard ratio, 2.25; 95% CI, 1.46-3.46; p = 0.0002). Patients with CKD had higher SOFA scores than patients without CKD (8.9 ± 4.0 and 6.5 ± 3.4, respectively; p < 0.0001). Additionally, an analysis of organ-specific SOFA scores revealed higher scores in three organ systems (kidney, cardiovascular and coagulation). Patients with CKD have the highest 90-day mortality risk compared with patients without CKD or with other chronic medical conditions.
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http://dx.doi.org/10.1038/srep10539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4650757PMC
May 2015

Primary bacteraemia is associated with a higher mortality risk compared with pulmonary and intra-abdominal infections in patients with sepsis: a prospective observational cohort study.

BMJ Open 2015 Jan 6;5(1):e006616. Epub 2015 Jan 6.

Department of Anesthesiology, University Medical Center, Georg August University, Goettingen, Niedersachsen, Germany.

Objective: To investigate whether common infection foci (pulmonary, intra-abdominal and primary bacteraemia) are associated with variations in mortality risk in patients with sepsis.

Design: Prospective, observational cohort study.

Setting: Three surgical intensive care units (ICUs) at a university medical centre.

Participants: A total of 327 adult Caucasian patients with sepsis originating from pulmonary, intra-abdominal and primary bacteraemia participated in this study.

Primary And Secondary Outcome Measures: The patients were followed for 90 days and mortality risk was recorded as the primary outcome variable. To monitor organ failure, sepsis-related organ failure assessment (Sequential Organ Failure Assessment, SOFA) scores were evaluated at the onset of sepsis and throughout the observational period as secondary outcome variables.

Results: A total of 327 critically ill patients with sepsis were enrolled in this study. Kaplan-Meier survival analysis showed that the 90-day mortality risk was significantly higher among patients with primary bacteraemia than among those with pulmonary and intra-abdominal foci (58%, 35% and 32%, respectively; p=0.0208). To exclude the effects of several baseline variables, we performed multivariate Cox regression analysis. Primary bacteraemia remained a significant covariate for mortality in the multivariate analysis (HR 2.10; 95% CI 1.14 to 3.86; p=0.0166). During their stay in the ICU, the patients with primary bacteraemia presented significantly higher SOFA scores than those of the patients with pulmonary and intra-abdominal infection foci (8.5±4.7, 7.3±3.4 and 5.8±3.5, respectively). Patients with primary bacteraemia presented higher SOFA-renal score compared with the patients with other infection foci (1.6±1.4, 0.8±1.1 and 0.7±1.0, respectively); the patients with primary bacteraemia required significantly more renal replacement therapy than the patients in the other groups (29%, 11% and 12%, respectively).

Conclusions: These results indicate that patients with sepsis with primary bacteraemia present a higher mortality risk compared with patients with sepsis of pulmonary or intra-abdominal origins. These results should be assessed in patients with sepsis in larger, independent cohorts.
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http://dx.doi.org/10.1136/bmjopen-2014-006616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4289738PMC
January 2015

The regulatory toll-like receptor 4 genetic polymorphism rs11536889 is associated with renal, coagulation and hepatic organ failure in sepsis patients.

J Transl Med 2014 Jun 21;12:177. Epub 2014 Jun 21.

Department of Anesthesiology, University Medical Center, Georg August University, D-37075 Goettingen, Germany.

Background: Toll-like receptor 4 (TLR4), a lipopolysaccharide (LPS) receptor complex signal-transducing molecule, plays a crucial role in sensing LPS from gram-negative bacteria. TLR4 signaling pathway activation by LPS plays a major role in sepsis pathogenesis. A single nucleotide polymorphism, rs11536889, in the 3'-untranslated region of the TLR4 gene is thought to affect TLR4 translation. This study aimed to investigate whether organ failure in sepsis patients is related to the TLR4 rs11536889 genotype.

Methods: Adult Caucasian patients with sepsis from the intensive care unit of a university medical center were followed up for 90 days, and organ failure was recorded as the primary outcome variable. Blood samples were collected at enrollment for TLR4 rs11536889 genotyping. Sepsis-related organ failure assessment (SOFA) scores were quantified at sepsis onset and throughout the observational period to monitor organ failure.

Results: A total of 210 critically ill patients with sepsis were enrolled into this study. Wild-type GG was compared to GC/CC. During their stay in the intensive care unit, GG patients presented significantly higher SOFA scores than did C allele carriers (7.9 ± 4.5 and 6.8 ± 4.2, respectively; p = 0.0005). Analysis of organ-specific SOFA sub-scores revealed significant differences in three organ systems: renal, coagulation and hepatic (p = 0.0005, p = 0.0245 and p < 0.0001, respectively). Additionally, the rs11536889 polymorphism was associated with a higher incidence of gram-negative infections.

Conclusions: These results offer the first evidence that TLR4 rs11536889 is a useful marker of organ failure in patients with sepsis.
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http://dx.doi.org/10.1186/1479-5876-12-177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4085654PMC
June 2014

Ninety-day survival rate of patients with sepsis relates to programmed cell death 1 genetic polymorphism rs11568821.

J Investig Med 2014 Mar;62(3):638-43

From the Departments of *Anesthesiology, Emergency and Intensive Care Medicine, †Thoracic and Cardiovascular Surgery, ‡General and Visceral Surgery, §Medical Statistics, and ∥Gastroenterology and Endocrinology, University Medical Center Goettingen, Goettingen, Germany.

Background: Sepsis is a life-threatening condition. Programmed cell death 1 protein (PD-1), a negative costimulatory molecule, is suggested to be involved in pathogenesis as mortality is associated with high expression and as neutralizing antibodies improve survival in a mouse model. The PD-1 gene harbors an intronic single-nucleotide polymorphism, rs11568821, which is located in a transcription factor-binding site and supposed to affect PD-1 transcription.

Objective: This study aimed at investigating whether mortality (90-day) among patients with sepsis associates with PD-1 rs11568821 genotypes.

Methods: Adult white patients with sepsis from the surgical intensive care units of a university medical center were followed up for 90 days, and mortality was recorded as primary outcome variable. Blood samples were taken for PD-1 rs11568821 genotyping. Sequential Organ Failure Assessment scores increased at enrollment and during the observation period to monitor morbidity.

Results: Two hundred nineteen critically ill patients with sepsis were enrolled in this investigation. Ninety-day mortality was significantly higher among G homozygotes than among A allele carriers (P = 0.0032). During intensive care unit stay, G homozygotes experienced higher Sequential Organ Failure Assessment scores (P < 0.001) and a higher demand of vasopressor therapy (P = 0.0107).

Conclusions: Data provide first associative evidence for PD-1 rs11568821 as a prognostic indicator in patients with sepsis.
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http://dx.doi.org/10.2310/JIM.0000000000000059DOI Listing
March 2014