Faculty Bibliography

BACKGROUND:Hyperthermia (heating to 43 °C) activates the innate immune system and improves bladder cancer chemosensitivity. OBJECTIVE:To evaluate the tissue penetration and safety of convective hyperthermia combined with intravesical mitomycin C (MMC) pharmacokinetics in live porcine bladder models using the Combat bladder recirculation system (BRS). METHODS:Forty 60 kg-female swine were anesthetized and catheterized with a 3-way, 16 F catheter. The Combat device was used to heat the bladders to a target temperature of 43 °C with recirculating intravesical MMC at doses of 40, 80, and 120 mg. Dwell-heat time varied from 30-180 min. Rapid necropsy with immediate flash freezing of tissues, blood and urine occurred. MMC concentrations were measured by liquid chromatography tandem-mass spectrometry. RESULTS:The Combat BRS system was able to achieve target range temperature (42-44 °C) in 12 mins, and this temperature was maintained as long as the device was running. Two factors increased tissue penetration of MMC in the bladder: drug concentration, and the presence of heat. In the hyperthermia arm, MMC penetration saturated at 80 mg, suggesting that with heating, drug absorption may saturate and not require higher doses to achieve the maximal biological effect. Convective hyperthermia did not increase the MMC concentration in the liver, heart, kidney, spleen, lung, and lymph node tissue even at the 120 mg dose. CONCLUSIONS:Convective bladder hyperthermia using the Combat BRS device is safe and the temperature can be maintained at 43 °C. Hyperthermia therapy may increase MMC penetration into the bladder wall but does not result in an increase of MMC levels in other organs.

Background: Patients with respiratory failure who require prone positioning are not considered good candidates for PD due to the concerns for increased intra-abdominal pressure, impaired diaphragmatic movement, and leaking of peritoneal fluid. We addressed the COVID-related AKI (CRAKI) surge for renal replacement therapy (RRT) by initiating an acute PD program at Bellevue Hospital including prone patients.
Method(s): All patients were in the ICU with COVID related hypoxic respiratory failure and acute kidney injury (AKI). 6/35 patients who received PD were treated for 16 hours per day in the prone position to improve oxygenation. The mean age was 54.6. The average BMI was 35.5. Patients were on mechanical ventilation 12-33 days. 3/6 patients were on CVVH however, switched to PD due to clotting. Patients were on PD for an average of 9.3 days. All PD catheters were placed at the bedside using an open cut down technique. PD was started the same day using manual exchanges. Dwell volume was gradually increased to 2 L. Exchanges were performed q1h while supine and q2h while prone, a total of 4-6 exchanges/day. The PD team coordinated timing with the prone team and ICU nurses to allow the continuation of the PD treatment. Patients were monitored clinically for abdominal distention and changes in respiratory mechanics.
Result(s): All 6 patients remained on PD for the duration of the hospitalization. There were no incidences of bowel injury, hemorrhage, exit-site infections, or peritonitis. None of the patients had any catheter malfunction. Leaking was addressed with temporarily reducing the dwell volume. Patients experienced slow draining which was due to kinking of the tubing during prone positioning. All patients were able to continue receiving PD without interruptions. Either no change or improvement in ABG and ventilator settings was noted after prone positioning and PD.
Conclusion(s): Due to COVID related surge, we saw a significant number of patients in the ICU with severe acute respiratory failure requiring prone positioning who also developed AKI requiring RRT. We were able to successfully provide acute PD in ventilator-dependent prone patients suffering from CRAKI. This required a team effort and some modifications in the conventional PD prescription. (Figure Presented)