复合微孔止血粉

World J Urol (2013) 31:523–527DOI 10.1007/s00345-011-0815-8ORIGINAL ARTICLEAthermal nerve sparing robot-assisted radical prostatectomy: initial experience with microporous polysaccharide hemospheres as a topical hemostatic agentRafael Nunez-Nateras · Kimberly J. Hurd · Erin N. Ferrigni ·Erik P. Castle · Paul E. Andrews · Mitchell R. HumphreysReceived: 26 April 2011 / Accepted: 13 December 2011 / Published online: 25 December 2011© Springer-Verlag 2011AbstractPurpose Microporous polysaccharide hemospheres (MPH) are hemostatic beads engineered from plant starch to acceler-ate the natural clotting cascade. The purpose of this report is to detail our initial experience with MPH as a topical hemo-static agent during robot-assisted radical prostatectomy (RARP).Methods We examined a single surgeon series of 30 con-secutive RARP’s dividing patients into MPH or non-MPH groups. The last ten procedures utilized the MPH, which were matched 1:2 to non-MPH procedures for comparison. Nerve-sparing procedures were performed when clinically indicated and all done athermally. All demographic data, length of operation, margin status, blood loss, change in hemoglobin, and need for blood transfusion were prospec-tively collected and analyzed.Results The baseline characteristics were the same. The post-operative decrease in hemoglobin was less in the MPH group (1.8g/dL MPH group vs. 3.2g/dL non-MPH). One patient in each group required a blood transfusion. Conclusions These preliminary W ndings support the role for MPH as a potential hemostatic agent during athermal nerve-sparing RARP.Keywords Topical hemostatic agent ·Robot-assisted radical prostatectomy ·Microporous polysaccharide hemospheres IntroductionThe advancement of minimally invasive surgical tech-niques has produced various challenges compared to tradi-tional open surgical approaches. These limitations include visualization, available instrumentation, spatial constraints, and accessibility that can all impede the ability of the sur-geon to e Y ciently control bleeding [1]. Acute blood loss has been the most frequently reported intraoperative com-plication during radical prostatectomy [2]. Because of the rich blood supply of the prostate pedicle and neurovascular bundles, there is potential for a signi W cant amount of bleed-ing during and after radical prostatectomy. Intraoperative bleeding cannot only a V ect perioperative morbidity and transfusion requirement, but it can also obscure the sur-geon’s W eld of vision of the prostatic apex and neurovascu-lar bundles impairing accurate surgical dissection [3].Preservation of the neurovascular bundles (NVB) and concomitant structures are of the utmost importance in appropriately selected patients during radical prostatectomy in order to preserve sexual function and continence [4]. Excess blood loss near or from the NVB can create pressure at the vesicourethral anastomosis after surgery that can dis-place or cause separation of the anastomosis thereby increasing the risk of a urine leak or alternatively can put undo strain on the NVB themselves. Excessive pressure on the NVB can impede continence, urinary function, and thus overall patient satisfaction [4]. Attempts to control blood loss can result in additional injury if thermal energy or neu-rotoxic hemostatic agents are used.Most surgeons attempt to limit neurovascular injury through a variety of techniques and methods. Limiting the amount of thermal injury near the NVB and minimizing the manipulation of these structures should be the endeavor of every surgeon. This often results in an accepted increase inR. Nunez-Nateras (&) · K. J. Hurd · E. N. Ferrigni · E. P. Castle · P. E. Andrews · M. R. HumphreysMayo Clinic Arizona, 5777 E Mayo Blvd,Phoenix, AZ 85054, USAe-mail: nunez.rafael@venous oozing from the NVB. Thus, many surgeons turn to topical hemostatic agents to prevent signi W cant blood loss, hematoma formation, and post-operative bleeding during nerve-sparing surgery. The ideal hemostatic agent should be non-immunogenic, economical, readily available, easy to deploy, and biodegradable.Microporous polysaccharide hemospheres (MPH: Meda-for Inc., Minneapolis, MN, USA) are plant-based polysac-charides that have been shown to be highly e V ective in achieving hemostasis [5]. MPH acts as molecular sieves dehydrating blood while concentrating individual blood components on their surface to accelerate the natural clot-ting cascade (Fig.1) [5]. MPH is currently approved by the US Food and Drug Administration (FDA) for use in surgery as an adjunctive hemostatic device to assist when control of capillary, venous, and arteriolar bleeding by pressure, ligature, and other conventional means is ine V ec-tive or impractical [6].The purpose of this research is to describe our initial experience with MPH used during athermal NVB preserva-tion during robot-assisted radical prostatectomy (RARP) in a single surgeon consecutive series.Materials and methodsAfter obtaining institutional review board (IRB) approval, a retrospective analysis was done of consecutive patients undergoing (transperitoneal) RARP for prostate cancer by a single surgeon. To examine those patients treated with MPH, they were compared to those that did not receive MPH in a 1:2 ratio, including all of the most recent cases done by the indicated surgeon (MRH). The same surgical technique was utilized in all cases, with varying levels of resident participation. When clinically indicated, the NVBs were spared using the criteria of a low grade Gleason score (·3+4), low tumor volume (no biopsy with greater than 50% involvement), and PSA <10ng/dL [7]. The prostate pedicles were controlled with the use of polymeric absorb-able clips and taken down in an athermal manner. The NVBs were dissected away from the prostate in all cases using sharp and blunt dissection as described by Gill et al.[8]. After the prostate and lymph nodes were placed in a specimen collection bag, MPH was applied to the NVBs and prostatic fossa using a rigid applicator by the bedside assistant. Following the running vesicourethral anastomo-sis, additional MPH was re-applied to the NVBs and lateral peri-prostatic areas. All patients were left with a 10 F round drain. Patients had cystograms performed at 7–10days post-operatively only if a resident performed the vesicoure-thral anastomosis.All data including age, weight, BMI, disease characteris-tics, pre-operative PSA, and medications taken were pro-spectively entered into our IRB approved database. All intra-operative and post-operative data including lymph nodes dissection, nerve sparing technique, pathologicalFig.1Representative illustra-tion of microporous hemo-spheres (MPH) and their relationship to the various com-ponents of human serum and the clotting cascadeanalysis, surgical time, estimated blood loss, change in hemoglobin, length of surgery, length of catheterization,and prostate size were collected as well. The data were ana-lyzed with commercially available software, SPSS ® version 10.0 statistical package (SPSS Inc., Chicago, IL, USA). All data were statistically analyzed with chi-square and Mann–Whitney U test for categorical and continuous variables,respectively. A two-sided P value <0.05 was considered as statistically signi W cant.ResultsPatient demographic data are in Table 1. Both groups were similar in make up and disease characteristics. Figure 2a–c represents the NVBs in a representative patient before and after MPH application as well as after the vesicourethral anastomosis, respectively. The surgical and pathological outcomes are presented in Table 2. The change in hemoglo-bin after 24h was much less in the MPH group, but this did not translate into a statistically signi W cant lower transfusion rate. While one patient in each group required a transfusion,the MPH patient actually bled from his left obturator fossa where MPH was not applied. The subsequent cross-sectional imaging from that patient’s scan revealed no hematoma or bleeding from the NVBs or prostatic fossa,Fig.3. Urinary extravasation was identi W ed in two patients in the non-MPH group requiring prolonged catheterization.There were no other complications identi W ed in the 30day peri-operative period.DiscussionTo our knowledge, this is the W rst study to detail the use of MPH during robot-assisted prostate surgery. The various techniques of nerve preservation during RARPs described in the literature signi W cantly improve functional outcomes for patients and are an important consideration for sexually active patients. However, due to the vascular investmentsof the prostate and NVB, there is a potential for bleeding during prostatectomy that can a V ect patient outcomes [8].This report describes our experience with a topical hemo-static agent (MPH) during athermal NVB preservation dur-ing RARP.The surgeries were all done by a single surgeon (MRH)who has been performing RARP since 2003, thereby decreasing the confounding e V ects of experience and learn-ing curve on the speci W c surgical technique. The age, BMI,ASA, pre-operative Gleason, and PSA scores were notTable 1Median patient demographic dataMPH groupNon-MPH group P Number of patients 1020Age (years)63 (51–77)64 (49–74)0.372BMI (kg/m 2)29 (22–36)29 (22–41)0.614ASA score2 (2–3) 2 (2–3)0.802Pre-operative PSA (ng/mL) 6.1 (3.7–9.4) 6.2 (1.3–16)0.721Pre-operative Gleason sum 7 (6–7)7 (6–8)0.911On aspirin at surgery (%)5 (50%)7 (35%)0.461Fig.2a Representative image of bilateral neurovascular preservation after robot-assisted radical prostatectomy.b Representative image of the same patient after application of the MPH to the neurovascular bun-dles.c Representative image of the same patient after the vesicoure-thral anastomosis with MPH application to the anterior urethral vesical junctionsigni W cantly di V erent in either group. Interestingly 50%,compared to 35%, of the MPH patients were on aspirin at the time of surgery thereby presumably increasing their potential risk for bleeding. However, the estimated blood loss and change in hemoglobin values favored the patients in the MPH group, regardless of concomitant use of anti-platelet therapy.One patient from each group required a blood transfu-sion. However, for the patient in the MPH group, this wasdue to a bleed originating in the obturator fossa, as a result of the lymphadenectomy where no MPH was applied. It is di Y cult to place the MPH in the right obturator fossa due to the location of the assistant ports during RARP. In the future, this could be over come by de-docking the robot and placing the applicator through a contralateral port.Other topical hemostatic agents have been used dur-ing surgeries to decrease bleeding. The topical applica-tion of BioGlue (CryoLife, Inc., Kennesaw, GA)generally requires a dry W eld prior to application [9].Therefore, acute, vigorous bleeding cannot be controlled by this agent. MPH can be applied to an actively bleed-ing source because of its unique mechanism [1, 5]. Evi-cel (Ethicon Inc., Somerville, NJ) is a human product that uses tranexamic acid. It has been reported to be neu-rotoxic and has caused convulsions, hyperexcitability,and death in rats [10]. Another concern of this product is that it has a prolonged preparation time of up to 40min to reconstitute [10]. QuickClot (Z-Medica Corp., Wal-lingford, CT) is composed of zeolite, a microporous crystalline aluminosilicate, which absorbs X uid causing an exothermic reaction [11]. This has been associated with necrosis and third degree thermal injury in the sur-rounding tissue and should never be used intracorparally [12]. MPH is not associated with any exothermic or known neurotoxicity.The active mechanism of hemoconcentrating endoge-nous clotting factors, which initiates particle swelling by osmotic forces, provides natural sca V olding on which a W brin matrix can form. The clot formed by the expanded MPH beads, platelets, and clotting proteins has been shown to be more resilient than a purely natural clot [13]. The MPH is then enzymatically broken down into small water-soluble fragments that leave no trace or radiographic evidence within 12h of application [14,15]. Because MPH is derived from a plant source, the risk of disease transmission or allergic reaction is mini-mal [15]. The production costs are theoretically low because it is manufactured from a readily available source.Despite the encouraging preliminary results, there are limitations to this study that should be considered. There were only 30 patients examined in this initial study, which hampers the power of this study. A larger randomized pro-spective trial is needed to validate these W ndings and better de W ne the role for MPH in prostate surgery. Long-term fol-low up is also needed as yet unrecognized e V ects due to MPH may have a negative impact on long-term NVB recovery. This data represent a single surgeon series at a training facility, and resident participation and experience could impact variations in surgical technique. However,direct supervision was present during all phases of every surgical procedure.Table 2Median surgical characteristics and outcomesaFour patients had positive margins: pT2c 3+3, pT3a 4+3, pT3a 5+4, and pT3b 4+3MPH groupNon-MPH group P Lymphadenectomy (%)10 (100%)20 (100%)–Nerve sparing –Bilateral 9/1016/20Unilateral 1/102/20None0/102/20Pathologic prostate size (g)62 (45–98)68 (33–118)0.328Post-op Gleason sum 7 (6–8)7 (6–9)0.476OR time (min)195 (126–335)239 (165–294)0.038Negative margins 100%80%a0.272EBL (mL)170 (50–400)220 (50–750)0.371Change in Hgb (g/dL) 1.8 (0.1–5) 3.2 (1.6–6.4)0.020Transfusion (%) 1 (10%) 1 (5%)0.999Length of stay (days) 1 (1-3) 1 (1-4)0.024Catheterization (days)9 (6–14)10 (7–30)0.514Fig.3Computed tomography image of the one patient in the MPH treated group that required a blood transfusion. Note the location of the bleed was from the left obturator fossa in the area of the node dissec-tion where no MPH was appliedConclusionsThis preliminary study indicates that MPH may be a useful adjunctive hemostatic agent during RARP. The changes in post-operative hemoglobin were minimized with no dis-cernible complications in the 30day peri-operative period. MPH appears to be a useful hemostatic tool that the urolo-gist should considering adding to their armamentarium. Acknowledgments The authors especially thank Desert Mountain C.A.R.E. for their support of prostate cancer research and this project.Con X ict of interest The authors have no con X icts of interest or W nancial relationships with any of the materials sited in this work. No additional outside funding was utilized to complete this work. The authors have maintained control of the primary data throughout all phases of this work.References1.Humphreys MR, Lingerman JE, Terry C et al (2008) Renal injuryand the application of polysaccharide hemospheres: a laparoscopic experimental model. J Endourol 22:1375–13812.Kordan Y, Barocas D, Altamar H et al (2010) Comparison oftransfusion requirements between open and robotic-assisted lapa-roscopic radical prostatectomy. BJU 106:1036–10403.Farnham S, Webster T, Herrell D et al (2006) Intraoperative bloodloss and transfusion requirements for robotic-assisted radical pro-statectomy versus radical retropubic prostatectomy. Urology 67:360–3674.Montorsi F, Salonia A, Nazareno S et al (2005) Improving thepreservation of the urethral sphincter and neurovascular bundlesduring open radical retropubic prostatectomy. Eur Urol 48:938–9455.Humphreys MR, Castle EP, Andrews PE et al (2008) Microporouspolysaccharide hemospheres for management of laparoscopic tro-car injury to the spleen. J Am Surg 195:99–1036.Food and Drug Administration Approval Letter (2006) Arista AHabsorbable Hemostat-P0500387.Fanning DM, Kay E, Fan Y et al (2009) Prostate cancer grading:the e V ect of strati W cation of needle biopsy Gleason score 4+3 as high or intermediate grade. BJU 105:631–6358.Gill IS, Ukimura O, Rubinstein M et al (2005) Lateral pedicle con-trol during laparoscopic radical prostatectomy: re W ned technique.J Urol 65:23–279.Nadler RB, Loeb S, Rubenstein RA et al (2006) Use of BioGlue inlaparoscopic partial nephrectomy. Urology 68:416–41810.Schwartz M, Madariaga J, Hirose R et al (2004) Comparison of anew W brin sealant with standard topical hemostatic agents. Arch Surg 139:1148–115411.Sefck J, McCormick AV (1999) Prediction of crystallization dia-grams for synthesis of zeolites. Chem Eng Sci 54:351312.Wright JK, Kalns J, Wolf EA et al (2004) Thermal injury resultingfrom application of a granular mineral hemostatic agent. J Trauma 57:224–23013.Dong Y, Schrader L, Drake JF et al (2001) Hemostatic does re-sponse of degradable starch microspheres (DSM45) as measured by thromboelastography. Presented at: Network for advancement of transfusion alternatives 2nd annual symposium, Berlin, Germany14.Hamdi G, Ponchel G (1999) Enzymatic degradation of epichloro-hydrin crosslinked starch microspheres by alpha-amylase. Pharm Res 16:867–87515.Murat FL, Ereth MH, Dong Y et al (2004) Evaluation of micropo-rous polysaccharide hemospheres as a novel agent in open partial nephrectomy: favorable experimental results in the porcine model.J Urol 172:1119–1122。