SCIENTIFIC ARTICLES

PROPHYLACTIC MINI-DOSE HEPARIN IN PATIENTS UNDERGOING RADICAL RETROPUBIC PROSTATECTOMY A Prospective

Trial

STEVEN \I!. BIGG, M.D. WIILIAM J. CATALONA.

X1.D.

k‘rom the Division of Urologic Surgery. Washington School of Medicine, St. Louis. Missouri

ABSTRACT.fwts

I!niversit!

We initiated

of pwiopmatiw

a prospwtiw, partially rmrlonkxd triul o.f I/W c;fprophylactic mini-dose hcparin 011 the irlcidencc of cli~li-

ca111/widen t pulmonary cnzholi. intruoperative blood loss. blood trunsfusiom. duration of postoperutive pelvic drainage. und lynphocele formution in 68 cogswutivc paticn t.c;undergoing radical retropuhic prostatw&y. W? twntd .32 paticwts with mini-dow hcpuril~ and .36 without it. WC>detwted pulrnmur!g cmholi in 4 (11 %) patirllts lrot treated with rnirli-dose hrparin urld ill 11011~ Iwaled with heparin (p = 0.052). Ancsthr?~siologists ostimatcd a II~~YII~illtruopcrutivc blood loss of 2.1.52 cc ill the hc~pariniwd patients cornparcd with 1 .HF% cc in controls (p = 0.2). At m time whell our poliq was to rcplaw ~111 blood loss. u:c transfuwd a ln~~clnof ,3..‘) Icnits to hcpurinixed patients clnd .3.2 rrnits to controls (p = 0.1). Pcrsisterl t lymphatic drainage requiring mow thus six days of closed suction druinage &wred in 12 of 32 (38 76) hcparinixtr’ putimts us compared with 4 of .36 (11 91) controls (13 = 0.01). We discorlti~rwd the study ufter 68 patients hccuusc of the morbidity ussociatcd tcith milli-t1o.w lrepurin. Bccuusc of the nssociuted morbidity uw do rwt recornnwnd the routine MC of lrlini-dose heparin in patients undergoing radicul ~,rostatectonl!i.

Patients undergoing major pelvic surgery, particularl!. those with cancer, have an increased risk of deep venous thrombosis and pulmonar\embolism developing. Fatal emboli have been reported to occur in O.‘i to 0.9 percent of all surgical patients. ’’ In cases of radical prostatectom); fatal ernboli have been reported to occur in 1.5 to 2.3 percent:’ 4 and non-fatal elnholi in 1.5 to *3.6:percent of patients.” (i There is a paucity of information concerning the value of mini-dose heparin prophylaxis in patients undergoing radical retropubic prostatectomv. In the present study. we evaluated prospect~vel~~ the risks and benefits of prophylactic mini-dose heparin in patients undergoing pelvic l\.mphadenectomq. and radical retropllbic prostatectom!. for prostate cancer.

Material

and X4cthods

We studied patients undergoing radical retropubic prostatectomy from Jul!, 1. 1988 to June 30, 1989 in this stud!: Wc attempted to randomize patients by having e\.clr!. other one receive mini-dose heparin. L)ue to administrative errors, but for no other reason. \vt’ inadvertently violated the randomization protocol on some occasions, resulting in 32 patients receiving mini-dose heparin and 36 not receiving it. One of us (U’JC) performed the operations as previously described7 at one hospital with the same group of anesthesiologists. We judged all patients to have\ clinically localized prostate cancer with negati\re findings on bone scans and normal acid phosphatase

Iicpclrin-trcc~tcd patients U.S.control group ______‘Total Estimated Clinically Apparent Transfusions Blood Loss Pulmonary Embolism (imits) ( ‘,;’) (4

TAHIJ: I.

Heparin Perioperative mini-dose heparin (n = 32) Controls (n = 36) p value

0 (0) 4 (11) x2 = 0.052

levels. All wore thigh-high sequential compression boots and elastic compression hose in the operating room, We discontinued the compression devices when the patients were ambulatory, usually eighteen hours postoperatively. We discontinued the elastic stockings before discharge. We encouraged patients to ambulate on the first postoperative day and discouraged prolonged sitting. Patients who were randomized to receive mini-dose heparin were given their first dose of 5,000 U subcutaneously two hours preoperatively and then the same dose every twelve hours until postoperative day 7 or the time of discharge. In most cases, the surgeon was aware of which patients received heparin. We did not inform the anesthesia personnel, but did not deliberately blind them. We documented the occurrence of thromboembolic complications with standard clinical tests only and did not perform isotope-labeled fibrinogen scans to detect subclinical events. We maintained our usual high index of suspicion for pulmonary emboli throughout the study. We evaluated patients with signs or symptoms suggestive of pulmonary embolus with arterial blood gases, chest x-ray film, electrocardiogram, and pulmonary ventilation-perfusion scan. Based on the clinical findings and the laboratory information, we determined a pre-test probability of a pulmonary embolus. We then used this to interpret the results of the ventilation-perfusion scan. At this point, we elected to manage the patient either with observation, anticoagulation for presumed pulmonary emholism, or pulmonary arteriography. Anticoagulation consisted of intravenous heparin to maintain the partial thromboplastin time (PTT) of sixty to eighty seconds followed b> oral dicumarol to maintain the prothrombin time (PT) of seventeen to nineteen seconds. The anesthesia team estimated the intraoperative blood loss from the volume of fluid (blood and urine) collected in the suction apparatus and on the surgical sponges. We also re-

310

2,1fj2 + 92X 1,886 k T46 1’ = 0.20

3.9 + 2.3 3.2 * 1.2 I’ = 0.10

Prolonged Closc~l Suction Drainage > 6 Days ( ‘G i 12132 (38) 3136 (11) xc 7 0.01

corded the total number of transfusions given during the hospitalization. At the time of this study, we routinely replaced most of the cstimated blood loss and usuall?. gave the patient back all of his banked autologous blood. We obtained complete blood counts preoperativelq and postoperatively as necessaqr until the counts were stable. We calculated the clifference in the hemoglobin between the preoperative and the final determination for the hospitalization (usually 1 to 7 days postoperatively). We routinely drained the pelvis postoperativel!, with two Jackson-Pratt closed suction drains which we left in place until postoperative day 5, unless the output over the preceding twenty-four hours was greater than SO cc. In this case, we left the drains in place until the output decreased below that amount. We recorded the incidence of postoperative bleeding, wound infection. and lymphocele formation. We performed a statistical analysis of the difference between means with the two-tailed ftest. We compared differences in proportions between groups with the chi-square test. Results We treated 68 patients with bilateral pc4vic lymphadenectomy and radical retropubic prostatectomy before discontinuing the study. mini-dose heparin Thirty-two (32) received (mean age, 67 years), and 36 did not receive heparin (mean age, 65 years). Four patients (11% ) not receiving mini-dose heparin had clinically evident pulmonary emboli while none of those receiving heparin had clinical evidence of pulmonary em holism (Table I). This difference approached significance (11 = 0.052, x2). Of those diagnosed with pulmonary emboli, all received anticoagulants without complications and all recovered uneventfullv. We documented the diagnosis of pulmonar!, embolism by pulmonar!. arteriogram in 2 patients. In the remaining patients, 1 had a high-

Estimated

Blood

Loss (ccl

Hepar~n

Group

Non Heparm Group

9

4

2

_--

0

_

n

2

I

5

3

Total Transfusion

(units)

probability ventilation-perfusion lung scban, and 1 had an intermediate-probability scan with a pretest probability that was very high due to tachycardia, hemoptysis. and h!yoxemia (paO* ==45 mm Hg). The anesthesia team estimated the clean intraoperative blood loss to be 1,886 cc in the non-heparinized group and 2.152 cc in the heparinized group (p = 0.2) (Figs. 1, 2). Fifty-nine patients banked autologous blood IIreoperatively. We transfused a mean of 3.9 U (S.D. = +2.3) to the heparinized patients and a mean of 3.2 U (S.D. = t 1.2) i-o the non-heparinized patients (p = 0.1) (Figs. 3. 4). The mean drop in hemoglobin was 2.4 mg/dL ( f 1.7) in the non-heparinized group and 2.5 group (p = mg/dL ( f 1.7) in the heparinized 0.69). The operating surgeon believed that patients receiving heparin required more effort to obtain adequate hemostasis. The average operative times were not significantly different between the two groups. For the last 10 patients enrolled, the operating surgeon \vas blinded as to the arm of the study in which the patient was enrolled, and he correctly predicted \vhich patients had or had not received hqjarin in 8 of the 10 patients. We defined prolonged l>,mphatic: d.raina(:e as that which required the Jackson-Pratt drains to remain in place for more than six days (the normal length of hospital stay). T~velve of 32 patients (38 ‘8,) in the heparinized group and 4 of 36 (11 5%) in the non-heparinized group had prolonged drainage (p = 0.01). One of the heparin-treated patients required readmission for percutaneous drainage of a lymphocele and another had heparinization stopped on postopdropped erative da) 2 when his hematocrit

l-k 6

from 28 percent to 18 percent. This patient also had a superficial wound infection as did one other heparinized patient. Thus there were 4 complications in 3 patients (9 % of 32) that may have been related to heparin prophylaxis. No patient in the control group experienced significant postoperative bleeding or a wound infection. Comment We initiated this prospective study to examine the risks and benefits of perioperative mini-dose heparin in radical prostatectomy patients. This group of patients is at an increased risk of deep venous thrombosis and pulmonary embolism due to the fact that they all had cancer and were undergoing major pelvic surgery. Several studies have shown that cancer patients have a higher incidence of deep venous thrombosis as detected by iodine 125 fibrinogen scanning. UJ It has been reported that patients undergoing radical retropubic prostatectomy have a 1.5 to 2.3 percent incidence of fatal pulmonary embolP4 and a 1.5 to 3.6 percent incidence of nonfatal emboli.“6 This represents a two to threefold increase in fatal pulmonary emboli compared with other surgical patients. These figures come from older studies and are higher than the current incidence of clinically apparent pulmonary emboli. For example, in our experience with over 503 consecutive patients undergoing radical prostatectomy using the anatomic approach,7 no patient has experienced a fatal postoperative complication. Nevertheless, prostate cancer patients do seem to be at higher risk and thus might be expected to benefit from effective prophylactic measures provided that the associated morbidity is low. Radical prostatectomy patients are also at increased risk for complications from mini-dose heparin prophylaxis. Three studies have reported significantly increased lymphocele formation after pelvic lymphadenectomy in patients receiving mini-dose heparin. lo I2 To our knowledge, no study has evaluated the effects of mini-dose heparin on hemorrhagic complications or the incidence of wound infections in radical prostatectomy patients. There are conflicting reports regarding the efficacy of mini-dose heparin in reducing deep venous thrombosis and pulmonary embolism, although the majority show it is beneficial. The largest published study is the International Multicenter Tria12.13 which showed a significant

decrease in the incidence of deep venous thrombosis, pulmonary emboli, and mortality from pulmonary embolus in patients treated with mini-dose heparin. The same conclusions were reached in an extensive review of 70 trials involving more than 15,000 general surgery, orthopedic, and urologic patients.’ Other studies with smaller numbers of patients either showed no benefit from mini-dose heparin* I4 or a decreased incidence of deep venous thrombosis, but no effect on the incidence of pulmonary emboli.‘” Other investigators reported no decreased incidence of deep venous thrombosis in subgroups of patients undergoing simple retropubic prostatectomy’” or those undergoing open bladder or prostate surgery.17 In spite of the conflicting results, the weight of evidence from the larger series and reviews seems convincing about the efficacy of mini-dose heparin in preventing deep venous thrombosis and pulmonar) emboli. In this study we observed a substantial reduction (p = 0.052) in the clinically apparent pulmonary emboli in patients treated with minidose heparin. However, the incidence of clinically evident pulmonary emboli in the nonheparinized group, 4 of 36 (11%) was higher than expected. This high incidence was probably due to chance alone. Our study group is too small to permit definitive conclusions concerning the effectiveness of mini-dose heparin in preventing pulmonary emboli in men treated with radical prostatectomy. The incidence of prolonged pelvic lymphatic drainage was significantly greater (p x0.01) in the heparin-treated patients. The heparinized group also included a patient who required readmission to the hospital for drainage of a lymphocele, 1 required the termination of heparin therapy because of a significant postoperative bleed, and 2 with superficial wound infections. We observed a trend toward more transfusions in the heparinized patients, but it was not statistically significant. It appeared that although mini-dose heparin may reduce thromboembolic complications, it also may be associated with more non-thromboembolic complications in patients undergoing radical prostatectomy and required a greater effort to achieve adequate hemostasis and lymphostasis; therefore, we elected to discontinue the study after 68 patients. It is difficult to accurately measure the intraoperative blood loss in patients undergoing radical prostatectomy. Once the bladder has

been opened, urine mixes with blood in the wound and their combined volume is measured in the suction apparatus. Intraoperative administration of large volumes of crystalloid and plasma expanders produces hemodilution and diuresis. The hemodilution lowers the hematocrit and the diuresis increases the amount of urine collected in the suction apparatus and absorbed by the laparotomy pads, thus artifactually increasing the estimated blood loss. The estimated blood loss in this study group in patients n,ot receiving heparin was approximatel) 400 mL, greater than the loss we reported previously in 130 patientsIR and also more than we measured in 146 subsequent patients. The reason for this discrepancy is unclear, but it may be related in part to changing transfusion policies. For example, in 146 consecutive patients operated on without mini-dose heparin since the completion of this study, the mean estimated blood loss was 1,575 + 711 (S.D.) cc and the mean intraoperative blood transfusions given was 1.72 :h 0.97 (S.D.) units. In those patients, the distribution of blood loss 5 1,000 cc in 24 percent. l.lOO--1,500 cc in 30 percent, 1,6002,000 cc in 27 percent, 2,100-2,500 cc in 12 percent. and >2,500 cc in 8 percent. Our current policy is to bank 4 units of autologous blood preoperatively, leaving most patients with a preoperative hematocrit of less than 35 percent. Then, early in the operation, we give 3 to 5 I, of crystalloid and volume expanders. After the prostate has been removed and hemostasis has been achieved, we transfuse only enough autologous blood to maintain the hematocrit above 24 percent. Based on this experience, we currently use mini-dose heparin only selectively in high-risk patients who have a prior history of thromboembolic complications. We continue to use thigh-high external compression boots which have been reported to significantly reduce deep venous thrombosis in urologic patients.R We also ambulation postoperaencourage \.igorous tively. With the use of these measures, the morbidit), associated with mini-dose heparin therap!: can be a\soided in the majority of patients.

Avenue .1SfiOAuduhm St. Louis, Missouri fi3110 (I) K. CA’l’,4LONA)

Prophylactic mini-dose heparin in patients undergoing radical retropubic prostatectomy. A prospective trial.

We initiated a prospective, partially randomized trial of the effects of perioperative prophylactic mini-dose heparin on the incidence of clinically e...
558KB Sizes 0 Downloads 0 Views