Publications by authors named "José Hinz"

58 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

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

Optimized Management of Endovascular Treatment for Acute Ischemic Stroke.

J Vis Exp 2018 01 18(131). Epub 2018 Jan 18.

Institute of Neuroradiology, University Medical Center Goettingen;

This manuscript describes a streamlined protocol for the management of patients with acute ischemic stroke, which aims at the minimization of time from hospital admission to reperfusion. Rapid restoration of cerebral blood flow is essential for the outcomes of patients with acute ischemic stroke. Endovascular treatment (EVT) has become the standard of care to accomplish this in patients with acute stroke due to large vessel occlusion (LVO). To achieve reperfusion of ischemic brain regions as fast as possible, all in-hospital time delays have to be carefully avoided. Therefore, management of patients with acute ischemic stroke was optimized with an interdisciplinary standard operating procedure (SOP). Stroke neurologists, diagnostic as well as interventional neuroradiologists, and anesthesiologists streamlined all necessary processes from patient admission and diagnosis to EVT of eligible patients. Target times for every step were established. Actually achieved times were prospectively recorded along with clinical data and imaging scores for all endovascularly treated stroke patients. These data were regularly analyzed and discussed in interdisciplinary team meetings. Potential issues were evaluated and all staff involved was trained to adhere to the SOP. This streamlined patient management approach and enhanced interdisciplinary collaboration reduced time from patient admission to reperfusion significantly and was accompanied by a beneficial effect on clinical outcomes.
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http://dx.doi.org/10.3791/56397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5908663PMC
January 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

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

Effects of Workflow Optimization in Endovascularly Treated Stroke Patients - A Pre-Post Effectiveness Study.

PLoS One 2016 30;11(12):e0169192. Epub 2016 Dec 30.

Department of Neuroradiology, University Medicine Goettingen, Goettingen, Germany.

Endovascular treatment of acute ischemic stroke has become standard of care for patients with large artery occlusion. Early restoration of blood flow is crucial for a good clinical outcome. We introduced an interdisciplinary standard operating procedure (SOP) between neuroradiologists, neurologists and anesthesiologists in order to streamline patient management. This study analyzes the effect of optimized workflow on periprocedural timings and its potential influence on clinical outcome. Data were extracted from a prospectively maintained university hospital stroke database. The standard operating procedure was established in February 2014. Of the 368 acute stroke patients undergoing endovascular treatment between 2008 and 2015, 278 patients were treated prior to and 90 after process optimization. Outcome measures were periprocedural time intervals and residual functional impairment. After implementation of the SOP, time from symptom onset to reperfusion was significantly reduced (median 264 min prior and 211 min after SOP-introduction (IQR 228-32 min and 161-278 min, respectively); P<0.001). Especially faster supply of imaging and prompt transfer of patients to the angiography suite contributed to this effect. Time between hospital admission and groin puncture was reduced by half after process optimization (median 64 min after versus 121 min prior to SOP-introduction (IQR 54-77 min and 96-161 min, respectively); P<0.001). Clinical outcome was significantly better after workflow optimization as measured with the modified Rankin Scale (common odds ratio (OR) 0.56; 95% CI 0.32-0.98; P = 0.038). Optimization of workflow and interdisciplinary teamwork significantly improved the outcome of patients with acute ischemic stroke due to a significant reduction of in-hospital examination, transportation, imaging and treatment times.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0169192PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5201273PMC
July 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

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

Remifentanil added to sufentanil-sevoflurane anesthesia suppresses hemodynamic and metabolic stress responses to intense surgical stimuli more effectively than high-dose sufentanil-sevoflurane alone.

BMC Anesthesiol 2015 18;15. Epub 2015 Jan 18.

Department of Anaesthesiology, Emergency and Intensive Care Medicine, University of Göttingen Medical School, Robert-Koch Str. 40, 37075 Göttingen, Germany.

Background: Even extremely high-doses of the potent opioid, sufentanil, cannot reliably suppress stress responses to intense surgical stimuli such as sternotomy. The chemically related opioid remifentanil with its different pharmacokinetics and binding affinities for delta- and kappa-opioid receptors might be more effective in attenuating these responses.

Methods: ASA I-III patients scheduled for a surgical procedure with sternotomy under balanced anesthesia (sevoflurane and sufentanil 3 μg.kg(-1) bolus, 0.017 μg.kg(-1).min(-1) infusion) were randomized into two groups. Patients in the study group were supplemented with remifentanil (2 μg.kg(-1) bolus, 2-7 μg.kg(-1).min(-1) infusion) starting ten minutes before sternotomy. Heart rate, arterial blood pressures, cardiac index, ejection fraction, systemic vascular resistance index (SVRI), total body oxygen uptake (VO2) and electric dermal response were measured and compared between the groups.

Results: 62 patients were studied (study group 32, control group 30). Systolic and mean arterial blood pressures, SVRI, VO2 and skin conductance increased during sternotomy and sternal spread in the control group but not in the study group. Systolic blood pressure increase: 7.5 ± 19 mmHg vs. -3.4 ± 8.9 (p = 0.005); VO2 increase: 31 ± 46% vs. -0.4 ± 32%; incidence of systolic blood pressure increase greater than 15 percent: 20% vs. 3% (p = 0.035) (control vs. study group).

Conclusion: High-dose remifentanil added to sevoflurane-sufentanil anesthesia suppresses the sympathoadrenergic response to sternotomy and sternal spread better than high-dose sufentanil alone.

Trial Registration:

Clinical Trial Number: DRKS00004327, August 31, 2012.
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http://dx.doi.org/10.1186/1471-2253-15-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4322556PMC
March 2016

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

Blood pressure response to combined general anaesthesia/interscalene brachial plexus block for outpatient shoulder arthroscopy.

BMC Anesthesiol 2014 30;14:50. Epub 2014 Jun 30.

Department of Anaesthesiology, Emergency and Intensive Care Medicine, University of Göttingen Medical School, Robert-Koch Str. 40, Göttingen 37075, Germany.

Background: Shoulder surgery is often performed in the beach-chair position, a position associated with arterial hypotension and subsequent risk of cerebral ischaemia. It can be performed under general anaesthesia or with an interscalene brachial plexus block, each of which has specific advantages but also specific negative effects on blood pressure control. It would be worthwhile to combine the advantages of the two, but the effects of the combination on the circulation are not well investigated. We studied blood pressure, heart rate, and incidence of adverse circulatory events in patients undergoing shoulder surgery in general anaesthesia with or without an interscalene block.

Methods: Prospective, randomised, blinded study in outpatients (age 18 to 80 years) undergoing shoulder arthroscopy. General anaesthesia was with propofol/opioid, interscalene block with 40 ml 1% mepivacaine. Hypotension requiring treatment was defined as a mean arterial pressure <60 mmHg or a systolic pressure <80% of baseline; relevant bradycardia was a heart rate <50 bpm with a decrease in blood pressure.

Results: Forty-two patients had general anaesthesia alone, 41 had general anaesthesia plus interscalene block. The average systolic blood pressure under anaesthesia in the beach-chair position was 114 ± 7.3 vs. 116 ± 8.3 mmHg (p = 0.09; all comparisons General vs. General-Regional). The incidence of a mean arterial pressure under 60 mmHg or a decrease in systolic pressure of more than 20% from baseline was 64% vs. 76% (p = 0.45). The number of patients with a heart rate lower than 50 and a concomitant blood pressure decrease was 8 vs. 5 (p = 0.30).

Conclusion: One can safely combine interscalene block with general anaesthesia for surgery in the beach-chair position in ASA I and II patients.

Clinical Trial Number: DRKS00005295.
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http://dx.doi.org/10.1186/1471-2253-14-50DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4083130PMC
October 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

Perioperative outcomes of cardiac surgery patients with ongoing ticagrelor therapy: boon and bane of a new drug.

Eur J Cardiothorac Surg 2014 Aug 12;46(2):198-205. Epub 2014 Jan 12.

Department of Thoracic and Cardiovascular Surgery, Georg-August-University Goettingen, Goettingen, Germany.

Objectives: Ticagrelor (Brilique®) is a novel reversible platelet inhibitor at P2Y12 receptor used in patients with acute coronary syndrome and patients undergoing percutaneous coronary interventions. Unlike clopidogrel (Plavix®), ticagrelor has a quicker offset of action, and therefore, it seems that platelet function recovers faster on discontinuation of therapy. These drugs sometimes cannot be stopped before coronary artery bypass grafting due to the risk of stent thrombosis or in case of emergency operations. Therefore, we investigated whether the continued preoperative use of ticagrelor influences the perioperative course of cardiac surgical patients.

Methods: The perioperative course and clinical outcomes of patients preoperatively receiving ticagrelor + acetylsalicylic acid (ASA) (n = 32) or clopidogrel + ASA (n = 49) until cardiac surgery, performed at University of Goettingen between January 2012 and December 2012, were studied. The study was designed as a retrospective observational study. The observation period started with the surgery and ended after 3 days. P < 0.05 was considered statistically significant.

Results: Preoperative data and intraoperative characteristics were almost similar among the groups. In the first 24 h, the median blood loss was 850 [780-1600] ml in the ticagrelor group and 680 [400-860] ml in the clopidogrel group (P = 0.0006). Furthermore, the median red blood cell transfusion (P = 0.0031), the median pooled platelet transfusion (P = 0.0012), the median prothrombin complex concentrate use (P = 0.0114) and the median fibrinogen use (P = 0.0118) were significantly higher in the ticagrelor group compared with the clopidogrel group. However, there was no statistical significance between the two groups regarding intensive care unit and hospital stay, mechanical ventilation time, incidence of acute kidney injury and mortality. Hence, a tendency towards more rethoracotomies due to bleeding in the ticagrelor group was observed (P = 0.0632).

Conclusions: In cardiac surgical patients who are treated with ticagrelor + ASA until surgery, ticagrelor therapy is associated with a significantly higher blood loss, a significantly higher use of blood products and coagulation factors and higher incidence of rethoracotomies for bleeding compared with patients treated with clopidogrel + ASA.
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http://dx.doi.org/10.1093/ejcts/ezt571DOI Listing
August 2014

The effect of changing the sequence of cuff inflation and device fixation with the LMA-Supreme® on device position, ventilatory complications, and airway morbidity: a clinical and fiberscopic study.

BMC Anesthesiol 2014 Jan 4;14. Epub 2014 Jan 4.

Department of Anaesthesiology, Emergency and Intensive Care Medicine, University of Göttingen Medical School, Robert-Koch Str, 40, 37075 Göttingen, Germany.

Background: The conventional sequence when using supraglottic airway devices is insertion, cuff inflation and fixation. Our hypothesis was that a tighter fit of the cuff and tip could be achieved with a consequently lower incidence of air leak, better separation of gastrointestinal and respiratory tracts and less airway morbidity if the device were first affixed and the cuff then inflated.

Methods: Our clinical review board approved the study (public registry number DRKS00003174). An LMA Supreme® was inserted into 184 patients undergoing lower limb arthroscopy in propofol-remifentanil anaesthesia who were randomly assigned to either the control (inflation then fixation; n = 92) or study group (fixation then inflation; n = 92). The cuff was inflated to 60 cmH2O. The patients' lungs were ventilated in pressure-controlled mode with 5 cmH2O PEEP, Pmax to give 6 ml kg-1 tidal volume, and respiratory rate adjusted to end-tidal CO2 of 4.8 and 5.6 kPa. Correct cuff and tip position were determined by leak detection, capnometry trace, oropharyngeal leak pressure, suprasternal notch test, and lube-tube test. Bowl and cuff position and the presence of glottic narrowing were assessed by fiberscopic examination. Postoperative dysphagia, hoarseness and sore throat were assessed with a questionnaire. Ventilatory impairment was defined as a tidal volume < 6 ml kg-1 with Pmax at oropharyngeal leak pressure, glottic narrowing was defined as an angle between the vocal cords under 16 degrees.

Results: The incidence of incorrect device position (18% vs. 21%), failed ventilation (10% vs. 9%), leak pressure (24.8 vs. 25.2 cmH2O, p = 0.63), failed lube-tube test (16.3% vs. 17.6%) and glottic narrowing (19.3% vs. 14.1%, p = 0.35) was similar in both groups (control vs. study, resp.). When glottic narrowing occurred, it was more frequently associated with ventilatory impairment in the control group (77% vs. 39%; p = 0.04). Airway morbidity was more common in the control group (33% vs. 19%; p < 0.05).

Conclusions: Altering the sequence of cuff inflation and device fixation does not affect device position, oropharyngeal leak pressures or separation of gastrointestinal and respiratory tracts. It reduces the incidence of glottic narrowing with impaired ventilation and also perioperative airway morbidity.
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http://dx.doi.org/10.1186/1471-2253-14-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3890616PMC
January 2014

The eNOS 894G/T gene polymorphism and its influence on early and long-term mortality after on-pump cardiac surgery.

J Cardiothorac Surg 2013 Oct 25;8:199. Epub 2013 Oct 25.

Department of Thoracic Cardiovascular Surgery, University of Göttingen, Robert-Koch Strasse 40, 37099 Göttingen, Germany.

Background: The eNOS 894G/T polymorphism (GG, GT, and TT) is associated with cardiovascular mortality and may influence cardiovascular diseases as a genetic risk factor. Moreover, this polymorphism has an impact on intraoperative hemodynamics during cardiac surgery with cardiopulmonary bypass (CPB). In this study, we analyzed the influence of this gene polymorphism on early clinical outcome in patients who underwent cardiac surgery with CPB. Also, we performed a 5-year follow-up, assessing the impact of this polymorphism on long-term mortality.

Method: 500 patients who underwent cardiac surgery with CPB between 2006 and 2007 were included in this prospective single centre study. Genotyping for the eNOS gene polymorphism was performed by polymerase chain reaction amplification.

Results: Genotype distribution of 894G/T was: GG 50.2%; GT 42.2%; TT 7.8%. Cardiovascular risk factors were equally distributed between the different genotypes of the eNOS 894G/T polymorphism. No significant difference among the groups was shown regarding Euroscore, SAPS II and APACHE II. Perioperative characteristics were also not affected by the genotypes, except for the consumption of norepinephrine (p = 0.03) and amiodarone (p = 0.01) which was higher in the GT allele carrier. The early postoperative course was quite uniform across the genotypes, except for mean intensive care unit length of stay which was significantly prolonged in GT carriers (p = 0.001). The five-year follow-up was 100% complete and showed no significant differences regarding mortality between the groups.

Conclusion: Our results show that the eNOS 894G /T polymorphism is not associated with early and late clinical outcome after cardiac surgery. Thus, this polymorphism can actually not help to identify high risk groups in the heterogeneous population of individuals who undergo cardiac surgery with CPB.
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http://dx.doi.org/10.1186/1749-8090-8-199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3819002PMC
October 2013

Reduced sevoflurane loss during cardiopulmonary bypass when using a polymethylpentane versus a polypropylene oxygenator.

Int J Artif Organs 2013 Apr 18;36(4):233-9. Epub 2013 Mar 18.

Department of Anesthesiology, Emergency Medicine and Intensive Care, Georg-August-University of Göttingen, Göttingen, Germany.

Purpose: The goal of this investigation was to examine the influence of two oxygenators with different membranes, made of either polypropylene (PPL) or polymethylpentane (PMP), on the plasma concentration of sevoflurane during cardiopulmonary bypass.

Methods: The concentrations of sevoflurane during cardiopulmonary bypass were examined in patient plasma, endotracheal tubes, cardiotomy reservoirs and the outlets of the heart-lung oxygenators in twenty patients who underwent elective heart surgery.

Results: The sevoflurane losses are smaller in cardiopulmonary bypass when using a polymethylpentane versus a polypropylene oxygenator. Ten minutes after beginning cardiopulmonary bypass, the sevoflurane plasma concentration in the PPL oxygenator group compared to the PMP oxygenator group fell significantly (PPL 0.48-1.79 (0.93) vs. PMP 0.80-2.15 (1.56) µL × 100 mL-1, p = 0.02). This difference persisted until ten minutes after the termination of cardiopulmonary bypass.

Conclusion: The results of this study show that using a polymethylpentane membrane oxygenator rather than a polypropylene oxygenator significantly reduces the losses of sevoflurane, resulting in higher plasma concentrations and greater depth of anesthesia.
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http://dx.doi.org/10.5301/ijao.5000208DOI Listing
April 2013