Phlebotomy resulting in controlled hypovolaemia to prevent blood loss in major hepatic resections (PRICE-1): a pilot randomized clinical trial for feasibility.

BACKGROUND: Major liver resection is associated with blood loss and transfusion. Observational data suggest that hypovolaemic phlebotomy can reduce these risks. This feasibility RCT compared hypovolaemic phlebotomy with the standard of care, to inform a future multicentre trial. METHODS: Patients undergoing major liver resections were enrolled between June 2016 and January 2018. Randomization was done during surgery and the surgeons were blinded to the group allocation. For hypovolaemic phlebotomy, 7-10 ml per kg whole blood was removed, without intravenous fluid replacement. Co-primary outcomes were feasibility and estimated blood loss (EBL). RESULTS: A total of 62 patients were randomized to hypovolaemic phlebotomy (31) or standard care (31), at a rate of 3·1 patients per month, thus meeting the co-primary feasibility endpoint. The median EBL difference was -111 ml (P = 0·456). Among patients at high risk of transfusion, the median EBL difference was -448 ml (P = 0·069). Secondary feasibility endpoints were met: enrolment, blinding and target phlebotomy (mean(s.d.) 7·6(1·9) ml per kg). Blinded surgeons perceived that parenchymal resection was easier with hypovolaemic phlebotomy than standard care (16 of 31 versus 10 of 31 respectively), and guessed that hypovolaemic phlebotomy was being used with an accuracy of 65 per cent (20 of 31). There was no significant difference in overall complications (10 of 31 versus 15 of 31 patients), major complications or transfusion. Among those at high risk, transfusion was required in two of 15 versus three of nine patients (P = 0·326). CONCLUSION: Endpoints were met successfully, but no difference in EBL was found in this feasibility study. A multicentre trial (PRICE-2) powered to identify a difference in perioperative blood transfusion is justified. Registration number: NCT02548910 ( http://www.clinicaltrials.gov).

ANTECEDENTES: La resección hepática mayor se asocia con pérdida de sangre y necesidad de transfusión. Datos observacionales sugieren que la flebotomía hipovolémica (hypovolaemic phlebotomy, HP) puede reducir estos riesgos. Este ensayo clínico aleatorizado (randomised clinical trial, RCT) de factibilidad comparó HP con el tratamiento estándar con el fin de proporcionar información para un futuro ensayo multicéntrico. MÉTODOS: Se reclutaron pacientes sometidos a resecciones hepáticas mayores entre junio 2016 y enero 2018. La aleatorización se realizó durante el intraoperatorio y los cirujanos eran ciegos al resultado de la asignación. Para la HP, se extrajeron 7-10 mL/kg de sangre total, sin reposición de líquidos intravenosos. Los resultados primarios fueron la factibilidad y la pérdida de sangre estimada (estimated blood loss, EBL). RESULTADOS: Un total de 62 pacientes se aleatorizaron a HP (n = 31) y a tratamiento estándar (n = 31), a un ritmo de 3,1 pacientes/mes, cumpliendo el co-objetivo primario de la factibilidad. La mediana de la diferencia de EBL fue 11 mL (P = 0,46). Entre los pacientes con alto riesgo de transfusión, la mediana de la diferencia de EBL fue 448 mL (P = 0,069). Los objetivos secundarios de factibilidad se consiguieron: reclutamiento (89%), cegamiento (98%), y objetivo de la flebotomía (7,6 ± 1,9 mL/kg). Los cirujanos que fueron cegados percibieron que la resección fue más fácil con la HP (52% versus 32%) y acertaron el uso de HP con una exactitud del 65%. No hubo diferencia significativa en las complicaciones globales (32% versus 48%), complicaciones mayores y transfusión. Entre aquellos pacientes de alto riesgo, la trasfusión se realizó en un 13% versus 33% (P = 0,33). CONCLUSIÓN: Se cumplieron los objetivos, pero no se identificó diferencia en EBL en este estudio de factibilidad. Ello justifica un ensayo multicéntrico (PRICE-2) con poder estadístico para identificar una diferencia en la transfusión de sangre perioperatoria.

Hyperbaric oxygen in the treatment of calciphylaxis: a case series.

BACKGROUND: Calciphylaxis, also referred to as calcific uraemic arteriolopathy, is a syndrome associated with end-stage renal disease (ESRD), and causes necrotic skin ulcers, often leading to a fatal outcome. Hyperbaric oxygen (HBO(2)) therapy has been used to enhance wound healing, but its role in the treatment of calciphylaxis is unclear. METHODS: We undertook a retrospective study of patients on renal replacement therapy with biopsy-proven calciphylaxis who were treated with HBO(2) between March 1997 and February 2000. RESULTS: Five patients were treated with HBO(2): three patients were on continuous ambulatory peritoneal dialysis (CAPD) and two were on chronic haemodialysis therapy. None of the patients had uncontrolled hyperparathyroidism and none underwent parathyroidectomy. The patients each received 25-35 treatments of HBO(2) at 2.5 atmospheres for 90 min per treatment. Two of these patients had complete resolution of extensive necrotic skin ulcers, with no adverse effects of HBO(2) therapy. Both had improvement in wound area transcutaneous oxygen pressure (P(tc)O(2)) with administration of 100% oxygen when measurements were taken at normobaric and hyperbaric pressures. In the other three patients receiving HBO(2), the skin lesions did not resolve. P(tc)O(2) was measured in two of these patients, neither of whom showed improvement with 100% oxygen administered at normobaric pressure. CONCLUSIONS: The data support a role for HBO(2) in the treatment of some patients with calciphylaxis, particularly as in the absence of uncontrolled secondary hyperparathyroidism there are few therapeutic options.

Systemic fat and thrombus embolization in patients undergoing total knee arthroplasty with regional heparinization.

A double-blind, randomized, controlled study was undertaken to determine if a technique of intraoperative anticoagulation would decrease the incidence or severity of venous embolization after tourniquet release during total knee arthroplasty. Sixty-six patients were randomized to receive either the heparin or placebo treatment. Transesophageal echocardiography was performed before and after tourniquet release to detect embolic material in the right atrium. Transient opacification of the right atrium was observed in all patients within the first 30 seconds after tourniquet release. Regional limb heparinization is not effective in reducing the intensity of right atrium opacification because much of the echogenic material was composed of fat rather than thrombus.

Cumulation characteristics of cisatracurium and rocuronium during continuous infusion.

PURPOSE: The dissimilar pharmacokinetic properties of cisatracurium (CIS) and rocuronium (ROC) predict different potential for drug cumulation when these drugs are administered by continuous infusion. A study was therefore undertaken to compare cumulation potential of CIS and ROC during surgical procedures of relatively long duration (2-4 hr). METHODS: Sufentanil/propofol-N2O anesthesia was administered to 40 ASA I and II adults. In a double-blind protocol, patients were randomly allocated to receive a continuous i.v. infusion of either CIS or ROC, titrated in progressive increments or decrements as required to achieve and maintain 95 +/- 5% depression of the T1 response of the adductor pollicis muscle, using a Datex NMT-100 Relaxograph EMG monitor applied at the wrist. At the end of surgery, 60 microg x kg(-1) neostigmine plus 15 microg x kg(-1) atropine were administered for reversal. RESULTS: The duration of infusion was 104 +/- 33 min in group CIS and 110 +/- 23 min in group ROC (P=NS). In both groups, a progressive decrease in potency-adjusted infusion rates was observed after 30 min, then stabilized beyond 60 min. When allowing for an initial period of stabilization, mean potency-adjusted infusion requirements were: CIS 0.81 +/- 0.02 microg x kg(-1) x min(-1) and ROC 5.58 +/- 1.94 microg x kg(-1) x min(-1). There were no differences between groups at any time with regard to potency-adjusted infusion requirements necessary to maintain 90-99% block (P=NS). However, drug costs/hr for maintenance of neuromuscular block were less with CIS ($3.57 +/- 0.09) than with ROC ($6.03 +/- 0.27), P < 0.001. CONCLUSION: When adjusted to equipotency, infusion requirements of CIS and ROC vary at similar rates during general anesthesia. Despite pharmacokinetic differences, neither drug demonstrates cumulation for infusion lasting up to 3.5 hr.