Analysis of sex-based differences in clinical and molecular responses to ischemia reperfusion after lung transplantation

Background Sex and hormones influence immune responses to ischemia reperfusion (IR) and could, therefore, cause sex-related differences in lung transplantation (LTx) outcomes. We compared men’s and women’s clinical and molecular responses to post-LTx IR. Methods In 203 LTx patients, we used the 2016 International Society for Heart and Lung Transplantation guidelines to score primary graft dysfunction (PGD). In a subgroup of 40 patients with blood samples collected before LTx (T0) and 6, 24, 48 (T48), and 72 h (T72) after lung reperfusion, molecular response to IR was examined through serial analysis of circulating cytokine expression. Results After adjustment, women had less grade 3 PGD than men at T48, but not at T72. PGD grade decreased from T0 to T72 more often in women than men. The evolution of PGD (the difference in mean PGD between T72 and T0) was greater in men. However, the evolution of IL-2, IL-7, IL-17a, and basic fibroblast growth factor levels was more often sustained throughout the 72 h in women. In the full cohort, we noted no sex differences in secondary clinical outcomes, but women had significantly lower peak lactate levels than men across the 72 h. Conclusions Men and women differ in the evolution of PGD and cytokine secretion after LTx: Women have a more sustained proinflammatory response than men despite a greater reduction in PGD over time. This interaction between cytokine and PGD responses warrants investigation. Additionally, there may be important sex-related differences that could be used to tailor treatment during or after transplantation.

Heart rate dynamics and lactate following high-intensity race-pace continuous vs interval workouts in highly trained athletes

PurposeThe present study aimed to compare the physiological responses of high-intensity race-pace continuous vs. interval workouts commonly used in middle-distance athletics, by means of analyzing post-exercise cardiac autonomic regulation and lactate.MethodsNineteen highly-trained 800-m male runners were asked to run a 600-m race-pace continuous workout and a 2 × 4 × 200-m interval training, counterbalanced and randomized within one week of difference. Blood lactate jointly with linear and nonlinear heart rate dynamics were assessed during the immediate 15-min recovery. Age-category (Under23-Senior vs. Juvenile-Junior) was considered as an inter-subject factor.ResultsPeak lactate was higher following the interval training (15.51 ± 0.99 vs 13.83 ± 1.77 mmol L−1; P < 0.05) whereas lactate removal was almost nonexistent 15 min after both workouts (between 0 and 16%). Vagal modulation (ln RMSSD and lnRMSSD to RR ratio) remained significantly depressed at the end of recovery following both workouts, although the alteration was larger following the interval training. Detrended Fluctuation Analysis evidenced a more random HR behavior (DFA1 closer to 0.5) during the first 9 min of recovery after the interval training, whereas no significant change was observed in heart rate complexity (SampEn). Neither were differences found in post-exercise lactate and HR dynamics as a function of age-category.ConclusionsHigh-intensity workouts commonly used in middle-distance athletics, both race-pace continuous and intervallic approaches, induce a large depression of vagal modulation in highly trained runners, although interval trainings appear to induce even a greater alteration of both linear and nonlinear HR dynamics and a higher post-exercise peak lactate.

Impact of Lactate Clearance on Early Outcomes in Pediatric ECMO Patients

Background and Objectives: Pediatric extracorporeal membrane oxygenation (ECMO) support is often the ultimate therapy for neonatal and pediatric patients with congenital heart defects after cardiac surgery. The impact of lactate clearance in pediatric patients during ECMO therapy on outcomes has been analyzed. Materials andMethods: We retrospectively analyzed data from 41 pediatric vaECMO patients between January 2006 and December 2016. Blood lactate and lactate clearance have been recorded prior to ECMO implantation and 3, 6, 9 and 12 h after ECMO start. Receiver operating characteristic (ROC) analysis was used to identify cut-off levels for lactate clearance. Results: Lactate levels prior to ECMO therapy (9.8 mmol/L vs. 13.5 mmol/L; p = 0.07) and peak lactate levels during ECMO support (10.4 mmol/L vs. 14.7 mmol/L; p = 0.07) were similar between survivors and nonsurvivors. Areas under the curve (AUC) of lactate clearance at 3, 9 h and 12 h after ECMO start were significantly predictive for mortality (p = 0.017, p = 0.049 and p = 0.006, respectively). Cut-off values of lactate clearance were 3.8%, 51% and 56%. Duration of ECMO support and respiratory ventilation was significantly longer in survivors than in nonsurvivors (p = 0.01 and p < 0.001, respectively). Conclusions: Dynamic recording of lactate clearance after ECMO start is a valuable tool to assess outcomes and effectiveness of ECMO application. Poor lactate clearance during ECMO therapy in pediatric patients is a significant marker for higher mortality.

Hyperlactataemia as a predictor of adverse outcomes post-cardiac surgery in neonates with congenital heart disease

Objective: To evaluate the discriminative ability of hyperlactataemia for early morbidity and mortality in neonates with CHD following cardiac surgery. Methods: Retrospective, observational study of neonates who underwent cardiac surgery on cardiopulmonary bypass at a tertiary care children’s hospital from June 2015 to June 2019. The primary predictor was lactate. The primary composite outcome was defined as ≥1 of the following: cardiac arrest or extracorporeal membrane oxygenation within 72 hours or 30-day mortality post-operatively. The secondary outcome was the presence of major residual lesions, according to the Technical Performance Score. Results: Of 432 neonates, 28 (6.5%) sustained the composite outcome. On univariate analysis, peak lactate within 48 hours, increase in lactate from ICU admission through 12 hours, and single ventricle physiology were significantly associated with the composite outcome. The peak lactate occurred at a median of 2.9 hours (interquartile range: 1, 35) before the event. Through multi-variable analysis, a multi-variable risk algorithm was created. Predicted probabilities demonstrated an increasing risk based on single ventricle status and delta lactate, ranging from 1.8% (95% CI: 0.9, 3.9) to 52.4% (95% CI: 32.4, 71.7). The model had good discriminative ability for the composite outcome on receiver operating characteristic analysis (area under the curve = 0.79; 95% CI: 0.75, 0.89). Moreover, a peak lactate of 7.3 mmol/l or greater was significantly associated with the presence of a major residual lesion (odds ratios: 5.16, 95% CI: 3.01, 8.87). Conclusions: We present a simple, two-variable model, including delta lactate in the immediate post-operative period and single ventricle status, to prognosticate the risk of early morbidity and mortality in neonates undergoing cardiac surgery for potential intervention.

The effects of hemodynamic management using the trend of the perfusion index and pulse pressure variation on tissue perfusion: a randomized pilot study

Background Intraoperative hemodynamic management is challenging because precise assessment of the adequacy of the intravascular volume is difficult during surgery. Perfusion index (PI) has been shown to reflect changes in peripheral circulation perfusion. Pulse pressure variation (PPV) reflects the preload responsiveness. The hypothesis of this study was that hemodynamic management using the trend of the PI and PPV would improve tissue perfusion. Methods This was a prospective, randomized, parallel design, single-blind, single-center pilot study. Patients undergoing elective open gynecological surgery requiring a direct arterial line were included. The patients were randomly allocated to two groups. The intervention group received hemodynamic management using the trend of the PI and PPV in an effort to improve tissue perfusion. The control group received hemodynamic management at the discretion of the anesthesia care provider. The primary outcome was the peak lactate level during surgery. The secondary outcomes were the duration of hypotension, intraoperative fluid balance, intraoperative urine output, and postoperative complication rate. Statistical analysis was performed using Student’s t test and Fisher’s exact test. A P value of < 0.05 was considered statistically significant. Results Although the intervention significantly decreased the duration of hypotension and intraoperative fluid balance, the peak lactate level was not different between the intervention group and the control group. Intraoperative urine output and postoperative complication rate were not different between the groups. Conclusion Hemodynamic management using the trend of the PI and PPV does not improve tissue perfusion in patients undergoing open gynecological surgery. Trial registration This trial was prospectively registered on a publicly accessible database (UMIN Clinical Trials Registry ID: UMIN 000026957. Registered 12 April 2017, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000030916).