Background
Acute kidney injury (AKI) in the intensive care unit is associated with significant mortality and morbidity

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Prevention of acute kidney injury and protection of renal function in the intensive care unit: update 2017 : Expert opinion of the Working Group on Prevention, AKI section, European Society of Intensive Care Medicine.

Acute kidney injury (AKI) occurs in 7% to 18% of hospitalized patients and complicates the course of 50% to 60% of those admitted to the intensive care unit, carrying both significant mortality and morbidity.[1][1] Even though many cases of AKI are reversible within days to weeks of occurrence, data

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Cardiac and Vascular Surgery-Associated Acute Kidney Injury: The 20th International Consensus Conference of the ADQI (Acute Disease Quality Initiative) Group.

Despite extensive research, no therapeutic interventions have been shown to prevent AKI, accelerate recovery of AKI, or reduce progression of AKI to CKD in patients. This failure in translation has led investigators to speculate that the animal models being used do not predict therapeutic responses in humans. Although this issue continues to be debated, an important concern that has not been addressed is whether improvements in preclinical study design can be identified that might also increase the likelihood of translating basic AKI research into clinical practice using the current models. In this review, we have taken an evidence-based approach to identify common weaknesses in study design and reporting in preclinical AKI research that may contribute to the poor translatability of the findings. We focused on use of N-acetylcysteine or sodium bicarbonate for the prevention of contrast-induced AKI and use of erythropoietin for the prevention of AKI, two therapeutic approaches that have been extensively studied in clinical trials. On the basis of our findings, we identified five areas for improvement in preclinical study design and reporting. These suggested and preliminary guidelines may help improve the quality of preclinical research for AKI drug development.

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Bridging Translation by Improving Preclinical Study Design in AKI

Acute kidney injury (AKI) is defined by a rapid decline in renal function. Regardless of the initial cause of injury, the influx of immune cells is a common theme during AKI. While an inflammatory response is critical for the initial control of injury, a prolonged response can negatively affect tissue repair. In this review, we focus on the role of macrophages, from early inflammation to resolution, during AKI. These cells serve as the innate defense system by phagocytosing cellular debris and pathogenic molecules and bridge communication with the adaptive immune system by acting as antigen-presenting cells and secreting cytokines. While many immune cells function to initiate inflammation, macrophages play a complex role throughout AKI. This complexity is driven by their functional plasticity: the ability to polarize from a "pro-inflammatory" phenotype to a "pro-reparative" phenotype. Importantly, experimental and translational studies indicate that macrophage polarization opens the possibility to generate novel therapeutics to promote repair during AKI. A thorough understanding of the biological roles these phagocytes play during both injury and repair is necessary to understand the limitations while furthering the therapeutic application.

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The role of macrophages during acute kidney injury: destruction and repair.

Background Part of the myocardial damage occurring during cardiac surgery is a consequence of reperfusion injury. Cyclosporine, a potent inhibitor of the opening of the mitochondrial permeability transition pore, attenuates reperfusion injury in patients with acute ST-segment elevation myocardial infarction. This study investigated whether the administration of cyclosporine just before the aortic cross-unclamping would reduce myocardial injury in patients undergoing aortic valve surgery. Methods This study was a monocentric, prospective, randomized, single-blinded, controlled trial. Sixty-one patients, scheduled for elective aortic valve surgery, were randomly assigned (computer-generated randomization sequence) to receive either an intravenous bolus of cyclosporine (2.5 mg/kg, cyclosporine group, n = 30) or normal saline (control group, n = 31) 10 min before aortic cross-unclamping. The primary endpoint was the 72-h area under the curve for cardiac troponin I. Results Both groups were similar with respect to baseline characteristics and aortic cross-clamping duration. A significant 35% reduction of area under the curve for cardiac troponin I was observed in the cyclosporine group compared with the control group (242 ± 225 vs. 155 ± 71 arbitrary units, mean ± SD; mean difference, -86.2 ± 42.5; 95% CI, -172.3 to -0.1; P = 0.03). Cyclosporine beneficial effect remained significant after adjustment for aortic cross-clamping duration in each group (mean difference, -88 ± 34, 95% CI, -157 to -19; P = 0.01). None of the treated patients had significant side effects (odds ratio, 0.64; 95% CI, 0.16 to 2.55; P = 0.52). Conclusions Cyclosporine administration at the time of reperfusion protects against reperfusion injury in patients undergoing aortic valve surgery. The clinical benefit of this protection requires confirmation in a larger clinical trial.

Cyclosporine Protects the Heart during Aortic Valve Surgery

Cardiac surgery-associated acute kidney injury (CSA-AKI) is a common complication following coronary bypass graft (CABG) surgery. Multi-factorial causes of CSA-AKI involve oxidative stress and inflammation. Erythropoietin (EPO) has been shown from many studies to have a reno-protective effect. The present study was conducted to examine the role of EPO in preventing CSA-AKI. This prospective, randomized, double-blind, placebo-controlled trial was conducted in the Cardiovascular and Thoracic Unit. One hundred patients randomly received either 200 U/kg of rHuEPO (n = 50) or saline (n = 50) intravenously three days before operation, and rHuEPO 100 U/kg or saline at operation time. The serum creatinine (SCr), estimated glomerular filtration rate (eGFR) and urine neutrophil gelatinase-associated lipocaline (NGAL) were measured in order to evaluate renal injury following CABG. The incidence of CSA-AKI was significantly lower in rHuEPO group (14%) when compared with the placebo group (38%; p < 0.01). The mean intensive care unit (ICU) and hospital stays of the rHuEPO group were significantly shorter than the placebo group (p < 0.01). Postoperative increases in SCr and decreases in eGFR were significantly lower in the rHuEPO group than the placebo group (p < 0.05). The mean urine NGAL in rHuEPO group was significantly lower than the placebo group at 3 hr, 6 hr, 12 hr and 18 hr after CABG (p < 0.05), respectively. Prophylaxis administration with intravenous rHuEPO before cardiac surgery decreased the incidence of CSA-AKI and urine NGAL with reduced days in ICU and hospital in elective CABG patients. ClinicalTrials.gov: NCT01066351

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Prophylaxis with erythropoietin versus placebo reduces acute kidney injury and neutrophil gelatinase-associated lipocalin in patients undergoing cardiac surgery: a randomized, double-blind controlled trial

Background: Therapeutic hypothermia has been recently approved to show benefits for neurological outcomes in patients after cardiac arrest. Application of both ECMO and surface cooling for treatment of therapeutic hypothermia has not yet been reported in the literature. We reported four cases that experienced in-hospital cardiac arrest during ECMO application treated with therapeutic hypothermia under surface cooling at Thammasat University Hospital. Case Reports: Four cases of in-hospital cardiac arrest during ECMO application were treated with therapeutic hypothermia under surface cooling with similar machine. The characteristics of each patient were described. The core temperature control during treatment was reported with temperature curves. A Glasgow coma score was used as index for neurological outcome Conclusion: Application of surface cooling together with extracorporeal membrane oxygenation (ECMO) is safe and feasible. Both devices facilitate treatment with therapeutic hypothermia in patients with post-cardiac arrest. Keywords: Therapeutic hypothermia, Cardiac arrest, Extracorporeal membrane oxygenation, Surface cooling

Therapeutic hypothermia with extracorporeal membrane oxygenation (ECMO) and surface cooling in post-cardiac arrest patients: 4 case reports.

Background: Hypertrophic scar development after median sternotomy wound in cardiac surgery patients is quite common in surgical practice and becomes a major concern nowadays. Objective: To compare cosmetic outcome between different suture materials and different suture techniques for skin closure in median sternotomy wound. Material and Method: A randomized clinical trial was conducted in 80 patients who underwent cardiac surgery in Thammasat University Hospital, Thailand. In respect of the materials and the techniques used to suture the skin, the patients were randomly allocated to four groups. In group 1, the skin was closed with subcuticular running 4-0 Poliglecaprone 25 (Monocryl). In group 2, the skin was closed with subcuticular running 4-0 Polydioxanone (PDS). In group 3, the skin was closed with subcuticular running 4-0 Poliglecaprone 25 (Monocryl) and running horizontal mattress 6-0 Nylon. In group 4, the skin was closed with subcuticular running 4-0 Polydioxanone (PDS) and running horizontal mattress 6-0 Nylon. Postoperative evaluation was performed at 2 and 6 weeks, 3 and 6 months follow-up visits. The scar was analyzed in three parts: upper, middle and lower one third of the sternal wound. The outcome measures for surgical wound were width, height and overall appearance of the scar using the Vancouver scar scale (VSS). A linear visual analogue score (VAS) was preformed to assess pain and itch. Results: At 6 months, there were no significant differences between 4 groups of patients in every parameters (width, height, VSS, pain score and itch score) at three different wound sites (upper, middle and lower). There was a statistically significant and progressive increase in scar stretching, height and total VSS from top to bottom of the sternum with the same pattern in all groups of patients (p<0.05). At 6 months, scar showed a statistically significant difference in width when compares to 6 weeks and 3 months (p<0.001).Female had a statistically significant difference of scar stretching at upper two third of the sternum (p<0.05). Female scar width was approximately 2 folds greater than male patient. During follow-up in group 3, two patients died postoperatively due to multi-organ failure and one patient developed wound infection. Conclusion: There were no significant differences in cosmetic outcomes between different suture materials and different suture techniques. Keywords: Polydioxanone, Poligiecaprone 25, Running horizontal mattress, Hypertrophic scar development, Median sternotomy wound

A randomized trial between different suture materials (polydioxanone vs. poliglecaprone 25) and different suturing techniques (running subcuticular suture alone vs. with running horizontal mattress) in prevention of hypertrophic scar development in median sternotomy wound.

Objective: Empyema thoracis is a frequent clinical problem and share in common a considerable potential for death and morbidity. Video-assisted thoracoscopic surgery [VATS] debridement or decortication become popular and increase the available treatment options. The authors aim is to determine the efficacy and outcome of VATS for management of empyema thoracis in adult patients. Material and Method: A retrospective study of all adult patient treated for empyema between June 2009 to Feb 2011 at Thammasat Hospital was conducted. Recorded data included demographic information, clinical presentation, laboratory data, microbiological data, operative details, postoperative course, follow-up data and complications. Results: A total of 23 patients [5 women, 18 men] underwent VATS debridement and decorication for treatment of empyema thoracis. Their mean age was 57 [35-90] years. 17 [74%] patients received preoperative drainage [percutaneous catheter drainage or tube thoracostomy] and mean duration of preoperative drainage was 7.6 [3-26] days. 8 [35%] patients had stage II empyema and underwent VATS debridement while 15 [74%] patients had stage III empyema underwent VATS decortication. Median postoperative hospital stay was 12.6 [7 48] days. Median time for postoperative intercostals drainage was 5 [3-30] days. Median follow-up time was 5 [1-20] months. Conversion rate to open thoracotomy for stage III empyema was only 13%. There were 3 postoperative complications [13%]: wound infection [n = 1], persistent space [n = 1] and recurrent infection [n = 1]. There was no intraoperative death and 2 [8%] perioperative death [< 30 days] which were mostly unrelated to surgery. Of the 23 patients, 20 patients [87%] achieved satisfactory results with treatment. Conclusion: VATS debridement and decortication is safe and effective treatment in the management of stage II and stage III empyema thoracis. Keywords: Video-assissted thoracoscopic surgery [VATS], Empyema thoracis, Decortication

Efficacy of video-assisted thoracoscopic surgery (VATS) for management of empyema thoracis.

Introduction:In our institute, we began using peripheral veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) in 2010, and peripheral veno-venous (VV) ECMO in 2015. This study aimed to des...

Clinical characteristics and outcomes of adults with peripheral extracorporeal membrane oxygenation in a developing country: A single center 8-year retrospective study.

Boonlawat Homvises

Papers

Prophylaxis with erythropoietin versus placebo reduces acute kidney injury and neutrophil gelatinase-associated lipocalin in patients undergoing cardiac surgery: a randomized, double-blind controlled trial

Therapeutic hypothermia with extracorporeal membrane oxygenation (ECMO) and surface cooling in post-cardiac arrest patients: 4 case reports.

A randomized trial between different suture materials (polydioxanone vs. poliglecaprone 25) and different suturing techniques (running subcuticular suture alone vs. with running horizontal mattress) in prevention of hypertrophic scar development in median sternotomy wound.

Efficacy of video-assisted thoracoscopic surgery (VATS) for management of empyema thoracis.

Clinical characteristics and outcomes of adults with peripheral extracorporeal membrane oxygenation in a developing country: A single center 8-year retrospective study.