Removal of meropenem and piperacillin during experimental hemoadsorption with the HA380 cartridge.

INTRODUCTION: Hemoadsorption can be used as adjunctive therapy for sepsis. However, there is limited evidence regarding its antibiotic removal. In this in vivo preclinical study, we aimed to evaluate the removal of meropenem and piperacillin with the HA380 hemoadsorption cartridge. METHODS: Healthy adult sheep (n = 6) received 2 g of meropenem, and 4 g of piperacillin intravenously for 30 minutes followed by hemoadsorption with a HA380 cartridge at a blood flow rate of 120 mL/min for 4 hours. The sorbent-based removal ratio, clearance, and mass removal were calculated at multiple time points. RESULTS: The sorbent-based removal ratio of meropenem decreased from 95.4% (SD 1.8) at 10 minutes to less than 20% at 4-hours of hemoadsorption. Its cumulative sorbent-based mass removal was 386.6 mg (SD 78.8) over 4 hours with 65.6 % (SD 7.1) occurring in the first 60 minutes. In contrast, the sorbent-based removal ratio of piperacillin decreased more gradually from 98.4% (SD 0.6) at 10 minutes to 37.4% (SD 7.2) at 4 hours. Its cumulative sorbent-based mass removal was 647.4 mg (SD 191.3) over 4 hours with 63.4% (SD 4.2) occurring in the first 60 minutes. The overall sorbent-based clearance of piperacillin was significantly greater than meropenem (Pgroup < 0.0001). CONCLUSION: Hemoadsoprtion with the HA380 cartridge removed meropenem and piperacillin throughout a 4-hour period, with high clearances at the start. Our findings can be used to inform dosing decisions during hemoadsorption in septic patients, there may be the need to consider increasing the doses of these antibiotics by 15-25 % to prevent underdosing.

Differential responses of cerebral and renal oxygenation to altered perfusion conditions during experimental cardiopulmonary bypass in sheep.

We tested whether the brain and kidney respond differently to cardiopulmonary bypass (CPB) and to changes in perfusion conditions during CPB. Therefore, in ovine CPB, we assessed regional cerebral oxygen saturation (rSO2 ) by near-infrared spectroscopy and renal cortical and medullary tissue oxygen tension (PO2 ), and, in some protocols, brain tissue PO2 , by phosphorescence lifetime oximetry. During CPB, rSO2 correlated with mixed venous SO2 (r = 0.78) and brain tissue PO2 (r = 0.49) when arterial PO2 was varied. During the first 30 min of CPB, brain tissue PO2 , rSO2 and renal cortical tissue PO2 did not fall, but renal medullary tissue PO2 did. Nevertheless, compared with stable anaesthesia, during stable CPB, rSO2 (66.8 decreasing to 61.3%) and both renal cortical (90.8 decreasing to 43.5 mm Hg) and medullary (44.3 decreasing to 19.2 mm Hg) tissue PO2 were lower. Both rSO2 and renal PO2 increased when pump flow was increased from 60 to 100 mL kg-1 min-1 at a target arterial pressure of 70 mm Hg. They also both increased when pump flow and arterial pressure were increased simultaneously. Neither was significantly altered by partially pulsatile flow. The vasopressor, metaraminol, dose-dependently decreased rSO2 , but increased renal cortical and medullary PO2 . Increasing blood haemoglobin concentration increased rSO2 , but not renal PO2 . We conclude that both the brain and kidney are susceptible to hypoxia during CPB, which can be alleviated by increasing pump flow, even without increasing arterial pressure. However, increasing blood haemoglobin concentration increases brain, but not kidney oxygenation, whereas vasopressor support with metaraminol increases kidney, but not brain oxygenation.

Vancomycin and Gentamicin Removal with the HA380 Cartridge during Experimental Hemoadsorption.

INTRODUCTION: Hemoadsorption has emerged as an adjunctive therapy for sepsis, but its impact on antibiotic levels remains poorly defined. We conducted an in vivo experimental study to investigate the removal of vancomycin and gentamicin during hemoadsorption using the HA380 cartridge, a novel styrene-divinylbenzene copolymer cartridge. METHODS: Six surgically prepared sheep were administered 2 g of vancomycin and 400 mg of gentamicin over 30 min, followed by a continuous infusion of vancomycin (20 mg/h). Hemoadsorption was implemented with a styrene-divinylbenzene copolymer HA380 cartridge at a blood flow of 120 mL/min. The removal ratio, sorbent-based clearance, and the mass removal rate were calculated for each time point. RESULTS: The mean 10-min vancomycin removal ratio exceeded 90% and declined to 68.0% at 30 min; 52.8% at 60 min, and 28.0% by 4 h. Due to constant plasma flow, clearance varied proportionally with the removal ratio. Over 4 hours, the total mass removal was 556 mg (SD 106.3). For gentamicin, the mean 10-min removal ratio was 96.9% and the final ratio at 4 h remained 53.0%, with clearances changing proportionately. The total mass removal of gentamicin was 138 mg (SD 26.6) over 4 h. The sorbent-based clearance of vancomycin was significantly lower than that of gentamicin (Pgroup < 0.0001). CONCLUSION: The novel HA380 sorbent cartridge appears safe and achieves significant vancomycin and gentamicin removal over a four-hour period. This information can be used by clinicians to guide their prescription and consider the additional dosing of at least an extra 25-35% amount in patients receiving HA380 hemoadsorption therapy during sepsis.

The effect of preoperative sodium-glucose cotransporter 2 inhibitors on the incidence of perioperative metabolic acidosis: A retrospective cohort study.

BACKGROUND: Sodium-glucose cotransporter 2 inhibitors are a novel class of anti-hyperglycemic agents. Although several cases of perioperative euglycemic diabetic ketoacidosis have been linked to these medications, the association remains unclear. This study aimed to examine the association between sodium-glucose cotransporter 2 inhibitor use and the incidence of perioperative metabolic acidosis with euglycemia, the surrogating outcome of perioperative euglycemic diabetic ketoacidosis. METHOD: This was a retrospective, matched cohort study, which was conducted in the intensive care unit of a tertiary care facility in Japan. We identified patients aged 20 years or older with diabetes mellitus who received pharmacologic therapy and were admitted to the intensive care unit after elective surgery between April 2014 and March 2019. We extracted the following data from the electronic medical record for matching: age, sex, surgery year, surgical site, hemoglobin A1c level, and prescription for sodium-glucose cotransporter 2 inhibitors. Eligible patients were divided into two groups, those who were prescribed sodium-glucose cotransporter 2 inhibitors (SGLT2-i group) and those who were not (control group). For each patient in the SGLT2-i group, we randomly selected four patients from the control group matched for the extracted characteristics. The primary outcome was the incidence of metabolic acidosis with an elevated anion gap and euglycemia. The secondary outcome was the lowest pH value of each patient during their ICU stay. RESULTS: A total of 155 patients were included in this study. Patients receiving sodium-glucose cotransporter 2 inhibitors had comparable characteristics to control participants; however, the proportions of patients undergoing dialysis were not similar. Metabolic acidosis with euglycemia was seen in 7/31 (22.6%) patients receiving sodium-glucose cotransporter 2 inhibitors and in 10/124 (8.1%) control patients (p = 0.047). CONCLUSIONS: This study shows that the use of sodium-glucose cotransporter 2 inhibitors is associated with a significantly higher incidence of metabolic acidosis with euglycemia. Patients receiving sodium-glucose cotransporter 2 inhibitors who are scheduled to undergo invasive surgical procedures should be closely monitored for the development of euglycemic diabetic ketoacidosis.

Efficacy of a newly developed bioabsorbable pancreatic clip for distal pancreatectomy in swine.

PURPOSE: At present, ≥ 20% of patients experience clinically relevant postoperative pancreatic fistula (POPF) after distal pancreatectomy (DP). METHODS: We developed a new bioabsorbable pancreatic clip (BioPaC) made of polycaprolactone that does not crush the pancreatic parenchyma during occlusion of the pancreatic stump. We confirmed the efficacy of this BioPac in a porcine DP model and compared it to a linear stapling device (Reinforce®). RESULTS: Pigs were killed at 1 month after DP. In the BioPaC group, all swine (n = 3) survived well without POPF. In the Reinforce® group (n = 2), one pig died early at postoperative day 7 with Grade C POPF (amylase 43 700 U/l), and the other survived until 1 month at scarification with biochemical leakage of POPF (amylase 3 725 U/l). Pathologically, the main pancreatic duct and pancreatic parenchyma were well closed by BioPaC. CONCLUSION: The newly developed BioPaC is effective in a porcine DP model.

Correlation between activated clotting time monitoring and heparin concentration measurement in a patient with antiphospholipid syndrome during cardiac valve surgery: a case report.

BACKGROUND: Anticoagulation management of patients with antiphospholipid syndrome (APS) undergoing cardiac surgery is challenging due to the prolongation of activated clotting time (ACT). Currently, no study has compared the utility of ACT monitoring using the Hemochron Jr. Signature+ and that of heparin concentration management using the Hemostasis Management System (HMS) Plus in patients with APS. CASE PRESENTATION: A 71-year-old woman with APS was scheduled to undergo an aortic valve replacement for aortic regurgitation. The ACT was measured using the Hemochron Jr. Signature+, and the heparin concentration was measured concurrently using the HMS Plus. ACT over 480 s corresponded to an adequate heparin concentration during cardiopulmonary bypass. The clinical course was uneventful, and no thrombotic or hemorrhagic complications were observed. CONCLUSION: In the present patient with APS, the Hemochron Jr. Signature+ was useful as an anticoagulation management during cardiac valve surgery.

Occurrence and incidence rate of peripheral intravascular catheter-related phlebitis and complications in critically ill patients: a prospective cohort study (AMOR-VENUS study).

BACKGROUND: The lack of precise information on the epidemiology of peripheral intravascular catheter (PIVC)-related phlebitis and complications in critically ill patients results in the absence of appropriate preventive measures. Therefore, we aimed to describe the epidemiology of the use of PIVCs and the incidence/occurrence of phlebitis and complications in the intensive care unit (ICU). METHODS: This prospective multicenter cohort study was conducted in 23 ICUs in Japan. All consecutive patients aged ≥ 18 years admitted to the ICU were enrolled. PIVCs inserted prior to ICU admission and those newly inserted after ICU admission were included in the analysis. Characteristics of the ICU, patients, and PIVCs were recorded. The primary and secondary outcomes were the occurrence and incidence rate of PIVC-related phlebitis and complications (catheter-related blood stream infection [CRBSI] and catheter failure) during the ICU stay. RESULTS: We included 2741 patients and 7118 PIVCs, of which 48.2% were inserted in the ICU. PIVC-related phlebitis occurred in 7.5% (95% confidence interval [CI] 6.9-8.2%) of catheters (3.3 cases / 100 catheter-days) and 12.9% (95% CI 11.7-14.2%) of patients (6.3 cases / 100 catheter-days). Most PIVCs were removed immediately after diagnosis of phlebitis (71.9%). Grade 1 was the most common phlebitis (72.6%), while grade 4 was the least common (1.5%). The incidence rate of CRBSI was 0.8% (95% CI 0.4-1.2%). In cases of catheter failure, the proportion and incidence rate per 100 intravenous catheter-days of catheter failure were 21% (95% CI 20.0-21.9%) and 9.1 (95% CI 8.7-10.0), respectively. CONCLUSION: PIVC-related phlebitis and complications were common in critically ill patients. The results suggest the importance of preventing PIVC-related complications, even in critically ill patients. TRIAL REGISTRATION: UMIN-CTR, the Japanese clinical trial registry (registration number: UMIN000028019 , July 1, 2017).