Sepsis in surgical patients: Personalized medicine in the future treatment of sepsis.

Sepsis results when a severe infection overwhelms the normal regulatory mechanisms of the immune system, resulting in a dysregulated host response characterized by new-onset organ failure. A wide range of infectious challenges can induce sepsis, resulting in an even wider range of maladaptive immune responses. This makes sepsis a syndromic diagnosis without a unifying, underlying molecular mechanism. The next step toward personalized medicine for sepsis is to resolve the heterogeneity across the universe of septic patients in order to establish pathobiologically homogenous sepsis "endotypes" that have uniformly defined changes in physiology and immunology. Defining the mechanisms of immune dysfunction within these endotypes will provide a roadmap for the application of immunomodulatory therapies for sepsis. This approach can drive in a paradigm shift in sepsis treatment, moving beyond supportive care and toward active efforts to restore normal immune function.

Five-Year Sustained Impact of a Thoracic Enhanced Recovery After Surgery Program.

BACKGROUND: Our thoracic enhanced recovery program (ERP) decreased the use of postoperative morphine equivalents and hospital costs 1 year after implementation at our tertiary center. The sustainability and potential increasing benefit of this program were evaluated. METHODS: From 2015 to 2021, we prospectively analyzed the outcomes of patients who underwent elective pleural, pulmonary, or mediastinal operations at our institution. Patients were separated on the basis of the incision (video-assisted thoracoscopic surgery [VATS] or thoracotomy). The ERP protocol was initiated on May 1, 2016, and includes preoperative education, carbohydrate loading, opioid-sparing analgesia, conservative fluid management, protective ventilation, and early ambulation. Outcomes of patients before (2015, pre-VATS and pre-thoracotomy) and after (May 1, 2016, to December 31, 2021, ERP-VATS and ERP-thoracotomy) ERP implementation were compared. RESULTS: The cohort included 1079 patients (pre-ERP era, n = 224 [21%]; ERP era, n = 855 [79%]). There was a median reduction of 1.5 hospital days per patient for ERP-thoracotomy and 1 hospital day per patient for ERP-VATS. Median postoperative morphine equivalents decreased in both groups (125 vs 45 mg, in ERP-thoracotomy; 84 vs 23 mg, ERP-VATS; P < .001), as did total admission cost ($32,118 vs $23,775, ERP-thoracotomy; $17,367 vs $11,560, ERP-VATS; P < .001). Median total fluid balance during the hospital stay decreased significantly. Rates of postoperative atrial fibrillation and urinary retention decreased across both subgroups. CONCLUSIONS: ERP for thoracic surgery is sustainable and has been demonstrated to improve patient outcomes, to decrease opioid use, and to lower hospital costs. Therefore, it has the potential to become the standard of care.

[The effect of obesity on the outcome of surgical aortic valve replacement for aortic stenosis].

INTRODUCTION: Our objective was to investigate the effect of obesity on short-term complications and long-term survival after surgical aortic valve replacement (SAVR) for aortic stenosis (AS). MATERIAL AND METHODS: A retrospective study on 748 patients who underwent SAVR for AS in Iceland 2003-2020. Patients were divided into groups based on body mass index (BMI): normal (18.5-24.9 kg/m2, n=190), overweight (25-29.9 kg/m2, n=339), obese (30-34.9 kg/m2, n=165) and severely obese (≥35 kg/m2, n=54). Six patients with BMI p<18,5 kg/m2 were excluded. Clinical information regarding patient history, risk factors, together with complications and 30-day mortality were collected from patient records. The four BMI groups were compared and long-term survival estimated with Kaplan-Meier plots and risk factors for long-term survival evaluated with Cox multivariate analysis. RESULTS: Severely obese patients were on average four years younger than patients with normal BMI, more often had risk factors for cardiovascular disease, and their EuroSCORE II was higher (5.3 vs. 4.4%, p=0.03). On the other hand, severely obese patients bled less the first 24 hours post-surgery, compared to normal BMI-patients (558 vs. 1091 ml, p<0.001), stroke was less frequent (0 vs 6.4%, p=0.03), but they more often experienced sternum dehiscence (5.6 vs 2.7%, p=0.04), deep sternal wound infection (3.7 vs 0%, p=0.04) and acute kidney injury (26.4 vs 15.2%, p=0.005). Thirty-day mortality and long-term survival did not differ significantly between the groups and BMI was not an independent predictor of long-term survival in multivariate analysis. CONCLUSIONS: The outcome for obese patients undergoing SAVR for AS is good and both short-term complications and long-term survival do not differ significantly from patients with a normal BMI. Therefore, a high BMI itself should not be a contraindication for SAVR due to AS.

Immediate and long-term need for permanent cardiac pacing following aortic valve replacement.

Introduction: Atrioventricular (AV) node conduction disturbances are common following surgical aortic valve replacement (SAVR), and in some cases the patient needs a permanent pacemaker (PPM) implantation before discharge from hospital. Little is known about the long-term need for PPM and the PPM dependency of these individuals. We determined the incidence of PPM implantation before and after discharge in SAVR patients. Methods: We studied 557 consecutive patients who underwent SAVR for aortic stenosis in Iceland between 2002 and 2016. Timing and indication for PPM were registered, with a new concept, ventricular pacing proportion (VPP), defined as ventricular pacing ≥90% of the time, being used to approximate pacemaker dependency. The median follow-up time was 73 months. We plotted the cumulative incidence of pacemaker implantation, treating death as a competing risk. Results: Of the 557 patients, 22 (3.9%) received PPM in the first 30 days after surgery, most commonly for complete AV block (n = 14) or symptomatic bradycardia (n = 8); Thirty-eight other patients (6.8%) had a PPM implanted >30 days postoperatively, at a median of 43 months after surgery (range 0‒181), most often for AV block (n = 13) or sick-sinus syndrome (n = 10). The cumulative incidence of PPM implantation at 1, 5, and 10 years postoperatively was 5.0%, 9.2%, and 12.3%, respectively. During follow-up, 45.0% of the 60 patients had VPP ≥90%. Conclusion: The cumulative incidence of permanent pacemaker implantation following SAVR was about 12% at 10 years, with every other patient having VPP ≥90% during follow-up. This suggests that AV node conduction disturbances extend significantly beyond the perioperative period.

Improved long-term outcome of surgical AVR for AS: Results from a population-based cohort.

BACKGROUND: The aim of this retrospective study was to determine changes in outcomes after surgical aortic valve replacement (SAVR) for aortic stenosis (AS) in Iceland over a 15-year period. METHODS: We included 587 patients who underwent SAVR for AS in Iceland during the period 2002-2016, with a total follow-up of 3245 patient-years. Short-term and long-term outcomes, 30-day mortality, and long-term survival (Kaplan-Meier) were analyzed. Univariate linear regression and univariate and multinomial logistic regression analyses were performed on preoperative and perioperative variables. Poisson regression analysis was used to evaluate changes in rates of short-term outcomes. RESULTS: Mean age was 71 years, 65.1% were males, and mean EuroSCORE II was 3.9. Mean preoperative aortic valve area increased significantly (0.013 cm2 /year; P < .001) and mean aortic cross-clamp time declined (108 minutes, 2.8 min/year; P < .001). The rate of complications decreased, including new-onset atrial fibrillation (60.9% overall, decreased by 3.1%/year, P = .02), acute kidney injury (17.1%, 7.6%/year, P < .001), and reoperation for bleeding (12.5%, 6.3%/year, P = .02). Operative mortality did not change (5.4%); nor did 1- and 5-year overall survival (92.5% and 81.6%, respectively). Notable long-term events were chronic heart failure (27.7 admissions/100 patient-years), embolic event (15.9/100 patient-years), and bleeding (13.0/100 patient-years). CONCLUSIONS: Results of SAVR in this well-defined nationwide cohort of patients in Iceland have improved. This may be related to the patients having less severe AS at the time of operation and shorter operating times, as reflected by lower rates of short-term complications. However, the rate of long-term complications did not change significantly, with prosthetic valve-specific events being rare.

[Early outcome of surgical aortic valve replacement for aortic stenosis in Icelandic females].

INTRODUCTION: Aortic valve replacement (AVR) for aortic stenosis (AS) is the second most common open-heart procedure performed in Iceland. The aim of this study was to analyze the early outcome of AVR among females in Iceland. MATERIALS AND METHODS: This was a retrospective study including 428 patients who underwent surgical AVR due to AS in Iceland from 2002-2013. Information was gathered from medical records, including pre- and postoperative results of echocardiography and complications. Overall survival was estimated (Kaplan-Meier) and logistic regression used to identify predictors of operative mortality. The median follow-up time was 8.8 years (0-16.5 years). RESULTS: Of the 428 patients, 151 were female (35.3%), that were on average 2 years older than men (72.6 ± 9.4 vs. 70.4 ± 9.8 yrs., p=0.020). Preoperative symptoms were similar, but women had significantly higher EurosSCORE II than men (5.2 ± 8.8 vs. 3.2 ± 4.6, p=0.002). Maximal pressure-gradient across the aortic valve was higher for women (74.4 ± 29.3 mmHg vs. 68.0 ± 23.4 mmHg, p=0,013) but postoperative complications, operative mortality (8.6% vs. 4.0%, p=0.068) and 5-year survival (78.6% vs. 83.1%, p=0.245) were comparable for women and men. Logistic regression analysis showed that female gender was not an independent predictor of 30-day mortality (OR 1.54, 95% CI 0.63-3.77). CONCLUSIONS: Females constitute one third of patients that undergo AVR for AS in Iceland. At the time of surgery females are two years older than men and appear to have a more significant aortic stenosis at the time of surgery. However, complication rates, operative mortality and long-term survival were comparable for both genders.

Favorable Survival after Aortic Valve Replacement Compared to the General Population.

BACKGROUND: A comparison was made between the long-term survival of patients undergoing aortic valve replacement (AVR) for aortic stenosis and of the general Icelandic population, using centralized registries. METHODS: A total of 366 AVR patients (231 males, 135 females; mean age 70.1 years) operated on for aortic stenosis in Iceland between 2002 and 2011 was included in the study. Concomitant coronary artery bypass grafting was performed in 54% of cases. Short-term complications and 30-day mortality were analyzed. The patients' overall survival was compared with the survival of Icelanders of the same age and gender. The median follow up was 4.7 years. RESULTS: A bioprosthesis was used in 81% of the patients; the median prosthesis size was 25 mm. Atrial fibrillation (68%) and acute kidney injury (23%) were the most common complications, and the 30-day operative mortality was 6%. Overall survival at one year and five years was 92% and 82%, respectively. There was no difference in survival between the surgical cohorts and expected survival of Icelanders of the same age and gender (p = 0.08), except for the first 30 postoperative days. CONCLUSIONS: Despite the significant rate of short-term complications, the long-term survival of patients undergoing AVR for aortic stenosis was good compared to the general population of the same age and gender. These results confirmed the value of AVR as an excellent treatment option for aortic stenosis, as it offers a normalization of the patients' life expectancy.

Acute kidney injury and outcome following aortic valve replacement for aortic stenosis.

OBJECTIVES: Most studies on acute kidney injury (AKI) following open-heart surgery have focused on short-term outcome following coronary artery bypass grafting. We reviewed the incidence, risk factors and outcome, including long-term survival, of AKI after aortic valve replacement (AVR) in a population-based cohort. METHODS: A retrospective review of 365 patients who underwent AVR for aortic stenosis during 2002-2011 was made. AKI was defined according to the RIFLE criteria. All patients requiring dialysis were followed up in a centralized registry. Risk factors for AKI were analysed with univariable and multivariable analysis, and survival was graphically presented with the Kaplan-Meier method. RESULTS: The rate of AKI was 82/365 (22.5%); 40, 28 and 14 patients belonging to the Risk, Injury and Failure groups, respectively. Preoperatively, 37 (45.1%) AKI patients had reduced kidney function. Transfusion of red blood cells, obesity and prolonged cardiopulmonary bypass time were independent risk factors for AKI. Acute postoperative dialysis was required in 15 patients (4.1%), and 1 patient developed dialysis-dependent end-stage renal disease. Major postoperative complications were more common in the AKI group (65 vs 22%, P < 0.001). The 30-day mortality rate in the AKI group was 18%, as opposed to 2% in the non-AKI group (P < 0.001), with a 5-year survival rate of 66 vs 87%, respectively (P < 0.001). In multivariable analysis AKI was an independent predictor of operative mortality [odds ratio = 5.89, 95% confidence interval (CI) = 1.99-18.91] but not of long-term survival (hazard ratio = 1.44, 95% CI = 0.86-2.42). CONCLUSIONS: More than 1 in 5 patients (22.5%) who underwent AVR developed AKI postoperatively. AKI was associated with higher morbidity and was an independent predictor of operative mortality. However, AKI was not a determinant of long-term survival.

Lower mortality following coronary arterial revascularization in patients taking statins.

OBJECTIVES: Numerous studies have suggested that statins have beneficial non-lipid-lowering effects, including reduction of systemic inflammatory response following surgery. We wanted to evaluate the effect of preoperative statin treatment on complications and operative mortality after coronary arterial revascularization. DESIGN: We performed a retrospective study of 720 consecutive patients who underwent on-pump coronary artery bypass grafting (CABG) (n = 513) or off-pump (OPCAB) (n = 207) in Iceland from 2002-2006. Patients taking statins preoperatively (n = 529) were compared with those not taking statins (n = 191). Predictors of complications and operative mortality were evaluated by univariate and multivariate analysis. RESULTS: Cardiovascular risk profiles were similar. However, hypertension was more common in the statin group but EuroSCORE was slightly lower. Operative mortality was significantly lower in patients taking statins (1.7% vs. 5.8%, p < 0.001). There were no significant differences in the incidence of major complications. Multivariate analysis showed that preoperative statin treatment was an independent predictor of lower operative mortality (OR = 0.33, p = 0.043), even after adjusting for EuroSCORE, acute operations, advanced age, or other medications. CONCLUSIONS: In this non- randomized study, patients taking statins had lower operative mortality than the controls after adjusting for multiple confounders. The reason for this might be linked to pleiotropic effects of statins.

[The outcomes of coronary artery bypass and aortic valve replacement in elderly patients]. / Árangur kransædahjáveituadgerda og ósædarlokuskipta hjá öldrudum.

OBJECTIVE: To study the outcome of open heart surgery in an increasing population of elderly patients in Iceland. MATERIAL AND METHODS: A retrospective study of patients (n=876) that underwent coronary artery bypass (CABG) or aortic valve replacement (AVR) for aortic stenosis in Iceland 2002-2006. Complication rates, operative mortality and long-term survival were compared between patients older (n=221, 25%) and younger (n=655, 75%) than 75 years. Long-term survival of the older group was compared to an age and sex matched reference population. RESULTS: Older patients had a higher incidence of atrial fibrillation (57% vs. 37%, p<0.001), stroke (5% vs. 1%, p=0.009) and operative mortality (9% vs. 2%, p<0.001) following CABG. Length of ICU stay was similar but total length of stay was one day longer in the older cohort. Following AVR, older patients had a higher incidence of atrial fibrillation (90% vs. 71%, p=0.006), ARDS (19% vs. 7%, p=0.04), myocardial infarction (21% vs. 8%, p=0.05) and operative mortality (11% vs. 2%, p=0.04). The ICU stay was a day longer and the total length of stay was about four days longer in the older cohort. A total of 75% of the older patients were alive five years after CABG, compared to 74% of the reference population (p=0.87). Similar numbers for AVR were 65% for the patients compared to 74% in the reference population (p=0.06). CONCLUSION: The rate of complications, operative mortality and length of hospital stay is higher in patients older than 75 years compared to younger patients. Survival of the older group of patients indicates good long-term results after open heart surgery for this patient cohort.

[Aortic valve replacement for aortic stenosis in Iceland 2002-2006: Long term complications and survival]. / Lokuskipti vegna ósædarlokuthrengsla á Islandi 2002-2006 - langtímafylgikvillar og lifun.

OBJECTIVE: To investigate long-term complications and survival following aortic valve replacement (AVR) in patients with aortic stenosis (AS) in Iceland. MATERIAL AND METHODS: Included were 156 patients (average age 71.7 yrs, 64.7% males) that underwent AVR for AS at Landspitali between 2002 and 2006. A mechanical prosthesis was used in 29 patients (18.6%) and a bioprosthesis in 127. Long-term complications and operation-related admissions were registered from hospital and outpatient records until April 1, 2010. Overall survival was estimated and compared with the Icelandic population of the same age and gender. RESULTS: The mean preop. EuroSCORE(st) was 6.9%, the max. transvalvular pressure gradient 74.1 mmHg and the left ventricular ejection fraction (LVEF) (57.2%). At six months following AVR the maximal pressure gradient was 19.8 mmHg (range; 2.5-38). Echocardiography results were not available for 23.6% of the patients 6 months postoperatively. In the follow-up period one in four patients was admitted due to valve-related problems. Re-admission rate was 6.0/100 patient-years (pt-y); most commonly due to cardiac failure (1.7/100 pt-y), emboli (1.6/100 pt-y), hemorrhage (1.6/100 pt-y), endocarditis (0.7/100 pt-y) and myocardial infarction (0.4/100 pt-y). Survival at 1 and 5 year was 89.7% and 78.2%, respectively, making survival comparable to the estimated survival of Icelanders of the same age and gender. CONCLUSIONS: The rate of long-term complications following AVR in Iceland is in line with other studies. The same applies to long-term survival, which was similar to that of the Icelandic population of the same age and gender. Key words: Aortic valve replacement, aortic stenosis, heart surgery, results, long-term complication, survival.

[Aortic valve replacement for aortic stenosis in Iceland 2002-2006: Indications and short term complications]. / Lokuskipti vegna óædarlokuprengsla á islandi 2002-2006: ábendingar og snemmkomnir fylgikvillar.

OBJECTIVE: Information on surgical outcome of aortic valve replacement (AVR) has not been available in Iceland. We therefore studied the indications, short-term complications and operative mortality in Icelandic patients that underwent AVR with aortic stenosis. MATERIAL AND METHODS: This was a retrospective study including all patients that underwent AVR for aortic stenosis at Landspitali between 2002 and 2006, a total of 156 patients (average age 71.7 years, 64.7% males). Short term complications and operative mortality (≤ 30 days) were registered and risk factors analysed with multivariate analysis. RESULTS: The most common symptoms before AVR were dyspnea (86.9%) and angina pectoris (52.6%). Preop. max aortic valve pressure gradient was on average 74 mmHg, the left ventricular ejection fraction 57.2% and EuroSCORE (st) 6.9%. The average operating time was 282 min and concomitant CABG was performed in 55% of the patients and mitral valve surgery in nine. A bioprothesis was implanted in 127 of the patients (81.4%), of which 102 were stentless valves, and a mechanical valve in 29 (18.6%) cases. The mean prosthesis size was 25.6 mm (range 21-29). Atrial fibrillation (78.0%) and acute renal injury (36.0%) were the most common complications and 20 patients (13.0%) developed multiple-organ failure. Twenty-six patients (17.0%) needed reoperation due to bleeding. Median hospital stay was 13 days and operative mortality was 6.4%. CONCLUSIONS: The rate of short term complications following AVR was relatively high, including reoperations for bleeding and atrial fibrillation. Operative mortality is twice that of CABG, which is in line with other studies.

[Impact of obesity on surgical outcomes following coronary artery bypass graft surgery]. / Tengsl offitu við árangur kransæðahjáveituaðgerða.

INTRODUCTION: Obesity has been related to increased postoperative morbidity and mortality following open-heart surgery. However, recent studies have shown no association or even a more favourable outcome in obese patients. This relationship was investigated in a well-defined cohort of patients that underwent myocardial revascularisation in Iceland. MATERIAL AND METHODS: A retrospective study including all patients that underwent isolated myocardial revascularisation in Iceland from 2002 to 2006. Altogether 720 patients were divided into two groups, an obese group, with BMI >30 kg/m2 (n=207, 29%), and a non-obese group with BMI ≤30 kg/m2 (n=513, 71%). Patient demographics, complications, operative mortality and long term survival of both groups were compared. RESULTS: Demographics were comparable between the groups. Obese patients were 2.4 years younger, more likely to use statins (83,3% vs. 71,2%, had a significantly lower EuroSCORE (4.3 vs. 5.0) but a slightly longer operation time. Pleural fluid was less often drained in obese patients (8.2 vs. 15.0%) but rates for other complications were similar in both groups, as was operative mortality ≤30 days (2.0% vs. 3.7%), 1 and 5 year survival. In a multivariate analysis obesity was not an independent risk factor for minor or major complications, operative mortality or long term survival. CONCLUSION: The rate of complications and operative mortality after myocardial revascularisation is not significantly higher in obese patients and the same applies to long term survival. This is true even after correcting for confounding factors in a multivariate analysis.