Nadir Oxygen Delivery on Bypass and Hypotension Increase Acute Kidney Injury Risk After Cardiac Operations

Magruder, J. Trent; Dungan, Samuel P.; Grimm, Joshua C.; Harness, H. Lynn; Wierschke, Chad; Castillejo, Stephen; Barodka, Viachaslau; Katz, Nevin M.; Whitman, Glenn J.R.

doi:10.1016/j.athoracsur.2015.05.059

Cited by 80 publications

(64 citation statements)

References 33 publications

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“…Pre-operative anemia reduces oxygen delivery and thus increases the risk of end-organ injury during cardiac surgery. [27] It is possible that both anemia and HCA temperature impact MC activation and related perioperative inflammatory responses through their role in I/R injury. On the other hand, RBC transfusions were associated with increased chymase responses in univariable, but not in multivariable analysis.…”

Section: Discussionmentioning

confidence: 99%

Mast cell activation and arterial hypotension during proximal aortic repair requiring hypothermic circulatory arrest

Kertai

Cheruku

et al. 2017

The Journal of Thoracic and Cardiovascular Surgery

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Objective Aortic surgeries requiring hypothermic circulatory arrest evoke systemic inflammatory responses that often manifest as vasoplegia and hypotension. Because mast cells can rapidly release vasoactive and pro-inflammatory effectors, we investigated their role in intraoperative hypotension. Methods We studied 31 patients undergoing proximal aortic repair with hypothermic circulatory arrest between June 2013 and April 2015 at Duke University Medical Center. Plasma samples were obtained at different intraoperative time-points to quantify chymase, IL6, IL8, TNFa, and white blood cell CD11b expression. Hypotension was defined as the area [minutes * mmHg] below a mean arterial pressure of 55 mmHg. Biomarker responses and their association with intraoperative hypotension were analyzed by two sample t test and Wilcoxon rank sum test. Multivariable logistic regression analysis was used to examine the association between clinical variables and elevated chymase levels. Results Mast cell-specific chymase increased from a median 0.97 [interquartile range, 0.01 to 1.84] pg/mg plasma protein at baseline to 5.74 [2.91 to 9.48] pg/mg plasma protein after instituting cardiopulmonary bypass, 6.16 [3.60 to 9.41] pg/mg plasma protein after completing of circulatory arrest and 7.64 [4.63 to 12.71] pg/mg plasma protein after weaning from cardiopulmonary bypass (each p<0.0001 vs baseline). Chymase was the only biomarker associated with hypotension during (p = 0.0255) and after cardiopulmonary bypass (p = 0.0221). Increased temperatures at circulatory arrest and low pre-surgical hemoglobin levels were independent predictors of increased chymase responses. Conclusion Mast cell activation occurs in cardiac surgery requiring cardiopulmonary bypass and hypothermic circulatory arrest and is associated with intraoperative hypotension.

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Section: Discussionmentioning

confidence: 99%

Mast cell activation and arterial hypotension during proximal aortic repair requiring hypothermic circulatory arrest

Kertai

Cheruku

et al. 2017

The Journal of Thoracic and Cardiovascular Surgery

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“…The principal inspiration for our study was data published by Ranucci and colleagues, 11 de Somer and colleagues, 10 and our group, 9 suggesting that nadir DO2 on CPB less than 225 to 272 mL O2/min/m 2 is associated with AKI. Although this pilot study of a bundled intervention cannot address the individual effect of any one GDP component, we would note that our perfusionists were able to achieve convincingly higher nadir DO2 levels, and the mechanism appeared to be via higher CPB flow rates.…”

Section: Discussionmentioning

confidence: 93%

“…In an attempt to avoid episodes of hypovolemic shock, we restricted retrograde autologous priming (RAP) use to a 10% decrease in MAP or NIRS readings, because such decreases have been associated with adverse outcomes. 17,18 Once the patient was on CPB, we sought to maintain DO2 greater than 300 mL O2/min/m 2 in keeping with the findings by our group and others about the importance of nadir DO2 and its association with AKI 9–11 ; we chose this conservative target of 300 mL O2/min/m 2 to remain safely above the published risk thresholds of 225 to 272 mL O2/min/m 2 . The perfusion staff targeted this range by increasing pump flows, as opposed to blood product transfusion.…”

Section: Methodsmentioning

confidence: 99%

“…Although it was counterintuitive, we sought to minimize vasopressor use out of concerns that it may have adverse effects on AKI rates. 9 Finally, we sought to limit the rate of rewarming after bypass, because high rewarming rates have been associated with neurocognitive dysfunction, increased glial fibrillary acid protein release, and potentially AKI. 25,26 The rate of rewarming was limited to 1°C every 5 minutes on bypass, with arterial temperatures not allowed to exceed 36.5°C unless specifically requested.…”

Section: Methodsmentioning

confidence: 99%

“…These have included nadir oxygen delivery (DO2) on CPB, at thresholds ranging from 225 mL O2/min/m 2 body surface area (BSA) to 272 mL O2/min/m 2 BSA. 9–11 To date, however, no clear guidelines or standards of care exist regarding many aspects of CPB. On the basis of these and other findings, in January 2015, several of our perfusionists, anesthesiologists, and surgeons adopted a set of goals as a quality improvement measure during CPB that they believed would reduce the postoperative incidence of AKI (see “Materials and Methods”).…”

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confidence: 99%

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A pilot goal-directed perfusion initiative is associated with less acute kidney injury after cardiac surgery

Magruder

Crawford

Harness

et al. 2017

The Journal of Thoracic and Cardiovascular Surgery

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Background We sought to determine whether a pilot goal-directed perfusion initiative could reduce the incidence of acute kidney injury after cardiac surgery. Methods On the basis of the available literature, we identified goals to achieve during cardiopulmonary bypass (including maintenance of oxygen delivery >300 mL O2/min/m2 and reduction in vasopressor use) that were combined into a goal-directed perfusion initiative and implemented as a quality improvement measure in patients undergoing cardiac surgery at Johns Hopkins during 2015. Goal-directed perfusion initiative patients were matched to controls who underwent cardiac surgery between 2010 and 2015 using propensity scoring across 15 variables. The primary and secondary outcomes were the incidence of acute kidney injury and the mean increase in serum creatinine within the first 72 hours after cardiac surgery. Results We used the goal-directed perfusion initiative in 88 patients and matched these to 88 control patients who were similar across all variables, including mean age (61 years in controls vs 64 years in goal-directed perfusion initiative patients, P = .12) and preoperative glomerular filtration rate (90 vs 83 mL/min, P = .34). Controls received more phenylephrine on cardiopulmonary bypass (mean 2.1 vs 1.4 mg, P < .001) and had lower nadir oxygen delivery (mean 241 vs 301 mL O2/min/m2, P < .001). Acute kidney injury incidence was 23.9% in controls and 9.1% in goal-directed perfusion initiative patients (P = .008); incidences of acute kidney injury stage 1, 2, and 3 were 19.3%, 3.4%, and 1.1% in controls, and 5.7%, 3.4%, and 0% in goal-directed perfusion initiative patients, respectively. Control patients exhibited a larger median percent increase in creatinine from baseline (27% vs 10%, P < .001). Conclusions The goal-directed perfusion initiative was associated with reduced acute kidney injury incidence after cardiac surgery in this pilot study.

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Renal and Cerebral Hypoxia and Inflammation During Cardiopulmonary Bypass

Jufar

Lankadeva

May

et al. 2021

Comprehensive Physiology

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Cardiac surgery-associated acute kidney injury and brain injury remain common despite ongoing efforts to improve both the equipment and procedures deployed during cardiopulmonary bypass (CPB). The pathophysiology of injury of the kidney and brain during CPB is not completely understood. Nevertheless, renal (particularly in the medulla) and cerebral hypoxia and inflammation likely play critical roles. Multiple practical factors, including depth and mode of anesthesia, hemodilution, pump flow, and arterial pressure can influence oxygenation of the brain and kidney during CPB. Critically, these factors may have differential effects on these two vital organs. Systemic inflammatory pathways are activated during CPB through activation of the complement system, coagulation pathways, leukocytes, and the release of inflammatory cytokines. Local inflammation in the brain and kidney may be aggravated by ischemia (and thus hypoxia) and reperfusion (and thus oxidative stress) and activation of resident and infiltrating inflammatory cells. Various strategies, including manipulating perfusion conditions and administration of pharmacotherapies, could potentially be deployed to avoid or attenuate hypoxia and inflammation during CPB. Regarding manipulating perfusion conditions, based on experimental and clinical data, increasing standard pump flow and arterial pressure during CPB appears to offer the best hope to avoid hypoxia and injury, at least in the kidney. Pharmacological approaches, including use of anti-inflammatory agents such as dexmedetomidine and erythropoietin, have shown promise in preclinical models but have not been adequately tested in human trials. However, evidence for beneficial effects of corticosteroids on renal and neurological outcomes is lacking.

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Nadir Oxygen Delivery on Bypass and Hypotension Increase Acute Kidney Injury Risk After Cardiac Operations

Cited by 80 publications

References 33 publications

Mast cell activation and arterial hypotension during proximal aortic repair requiring hypothermic circulatory arrest

Mast cell activation and arterial hypotension during proximal aortic repair requiring hypothermic circulatory arrest

A pilot goal-directed perfusion initiative is associated with less acute kidney injury after cardiac surgery

Renal and Cerebral Hypoxia and Inflammation During Cardiopulmonary Bypass

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