EFFICACITE ET TOLERANCE DE L’ENOXAPARINE DANS LA PREVENTION DES COMPLICATIONS THROMBO-EMBOLIQUES APRES CHIRURGIE LAPAROSCOPIQUE

Makni Amin MD | Magherbi H Magherbi H | El Héni A El Héni A | Mzoughi Z Mzoughi Z | Rebai W Rebai W | Daghfous A Daghfous A | Ftérich F Ftérich F | Ksantini R Ksantini R | Chebbi F Chebbi F | Jouini M Jouini M | Ammous A Ammous A | Kacem JM Kacem JM | Arfa N Arfa N | Khalfallah T Khalfallah T | Ben Safta Z Ben Safta Z |

La tunisie chirurgicale - 2017 ; Vol 2017

Resumé

Pré-requis: L’efficacité de l’Enoxaparine dans la prévention des complications thrombo-emboliques (CTE) après chirurgie laparoscopique n’a pas fait l’objet de beaucoup d’études dans la littérature.

But: Le but de ce travail est de démontrer l’éfficacité et la tolérance de l’administration de l’Enoxaparine en sous cutanée pour la prévention des CTE dans les suites de la chirurgie laparoscopique.

Matériel et méthodes: Nous rapportons une étude prospective qui s’est déroulée dans deux services de chirurgie digestive entre Mai 2010 et Février 2011 et qui a inclus tous les patients qui ont été opéré par voie laparoscopique. Nous n’avons inclus que les patients qui ont été mis en post-opératoire sous Enoxaparine en fonction de sa disponibilité à l’hôpital. Nous avons inclus au total 169 patients. Tous ces patients ont reçu la dose de 4000 UI/ jour en une seule prise en sous cutanée pour une durée de 10 jours.

Résultats: Aucun patient n’a présenté de CTE: thrombose veineuse profonde ou embolie pulmonaire. Il n’y avait pas de différence significative observée du taux de prothrombine et du taux des D-dimères évalués au 7ème jour post-opératoire. Aucune complications liées à le prescription d’héparine à bas poids moléculaire n’a été notée.

Conclusion: L’utilisation de l’Enoxaparine pour la prévention des complications thrombo-emboliques après chirurgie laparoscopique est sure, cependant l’efficacité nécessite une étude comparative avec d’autres molécules références disponible sur le marché.

Mots Clés

Laparoscopie, chirurgie, enoxaparine, complications thrombo-emboliques

Introduction :

Venous thromboembolism (VTE), including pulmonary embolism (PE) and deep venous thrombosis (DVT), is a major complication in patients who have undergone surgery [1]. Although these events are rare, they can be still associated with high mortality during the early postoperative period. Several known significant risk factors are responsible for the development of VTE, including female gender, advanced age, advanced-stage cancer, prolonged surgical duration, intrapelvic surgeries, varicose veins, immobilization, obesity, history of VTE, and a high number of chronic medical comorbidities [2-4]. In particular, patients undergoing curative abdominal cancer surgery are considered to be at a high risk for VTE [5]. In recent years, numerous abdominal surgical procedures have been laparoscopically performed, and these offer some advantages over conventional open incisional surgery, including decreased pain, quicker convalescence, and improved cosmesis. Nevertheless, this technique is still associated with a distinct morbidity. Moreover, the incidence of VTE associated with laparoscopic and open incisional surgery has been reported as almost equal [6, 7], but the abdominal insufflation used during laparoscopic procedures has been proposed to cause serum hypercoagulability of varying degrees and VTE secondary to venous stasis [8, 9].

The incidence of VTE following a major abdominal surgery without prophylaxis has been reported to be approximately 20%, and the reported incidence of symptomatic PE ranges from 0.5% to 1.6% [4, 10, 11]. Because VTE may rapidly lead to fatality, its prevention by early ambulation, intermittent pneumatic compression (IPC), or chemoprophylaxis is inevitable, particularly in patients with potential risk factors. However, there are no uniform guidelines for the use of chemoprophylaxis, and little evidence is available to justify a routine prophylactic anticoagulation treatment for laparoscopic surgery. Till date, to the best of our knowledge, there have been no randomized controlled trials addressing the issue of VTE prophylaxis in patients undergoing abdominal laparoscopic surgery.

In the present study, we have evaluated the validity of chemoprophylaxis with subcutaneous administration of enoxaparin for the prevention of VTE in abdominal laparoscopic surgery. This is the first report to evaluate detailed laboratory data changes in patients treated with enoxaparin after abdominal laparoscopic surgery and is considered to be clinically informative.

Article

MATERIALS AND METHODS

Study design and patient selection

This study was performed with the approval of the local institutional review board. Prior to treatment, we obtained verbal and written informed consent from all patients. We evaluated 188 consecutive patients, we excluded 19 patients (operated by laparotomy or by laparoscopy and required a conversion to laparotomy), finally we retained 169 patients [69 males and 100 females; age, 20–92 years (mean, 52 years); body mass index exceeding 25 kg/m2 in 35 cases (20%)] undergoing digestive laparoscopic surgery between May 2010 and February 2011. Of all the laparoscopic surgeries performed, 96 (57%) were in emergency [Acute peritonitis (n=28), acute cholelithiasis (n=66) and acute cholangitis (n=2)], the other 73 (43%) patients underwent an elective surgery [Mesh for hernia (n=56), colectomy for caner or inflammatory bowel disease (n=8), colorectal polyposis (n=4), Nisses procedure (n=2) and gastro-entreo-anastomosis (n=3)] (Table 1).

Postoperative thromboprophylaxis with a subcutaneous injection of enoxaparin (low molecular weight heparin, LMWH; 4000 UI once daily) and IPC was planned. Enoxaparin treatment was initiated more than 2 h after the removal of the epidural catheter at 24–36 h after surgery and continued for 10 consecutive days. IPC treatment using pneumatic compressive stockings was initiated on the day of the surgery and continued until patients were completely mobile. All patients were aggressively hydrated and were advised to ambulate within 24 h after surgery. Physical examinations for early detection of VTE and adverse events associated with hemorrhagic complications were performed whenever possible. In addition, hematological examinations (prothrombin time (PT) and D-dimer levels) were conducted before surgery and on day 7.

The statistical analysis

All parameters were listed in statistical software SPSS 17.0. Quantitative variables were expressed by their averages and standard deviations (SD). Categorical variables were expressed by their frequencies. It was used to compare qualitative variables X2 test (Fisher's exact correction for small numbers). It was used to compare quantitative variables Student's t test. A test was considered statistically significant for p <0.05. For the study of risk factors for surgical recurrence, it was initially based on a univariate study. In a second step, we had conducted a multivariate model using logistic regression to multiple variables expressed by their relative risk (RR). To test the independence of behavioral variables, we had used in the logistic regression variables that had a p <0.2 in the univariate analysis.

RESULTS

All laparoscopic surgeries were successful. The mean operative time was 80  min (from 30 to 180 min), and the estimated blood loss was 40 mL (from 0 to 1000 mL). According to the 8th American College of Chest Physicians (ACCP) Conference on Antithrombotic and Thrombolytic Therapy risk-group classification [12], 61, 4 and 104 patients were classified into low-, moderate- and high-risk groups, respectively. Thirteen patients (7.6%) had concurrent disease such as diabetes or hypertension. Six patients (3.5%) had a personal or familial history of prior VTE. Table 2 shows risk factors of VTE in the present study.

All patients were administered with postoperative prophylaxis using enoxaparin (4000 UI once daily for 10 days). Patients treated with enoxaparin did not develop symptomatic VTE or PE.

Our data from hematological examinations performed on day 7 demonstrated a significant decrease in PT (P < 0.0001) and a significant rise in D-dimer levels (P < 0.0001) compared with the data before surgery. These values did not exceed the normal range or were only marginally elevated and were not considered to pose problems in clinical practice. None of the patients had major bleeding complications or prolonged minor bleeding in this series.

DISCUSSION

VTE, with the potential sequela of PE, has been recognized as a fatal complication associated with any major abdominal surgery, and the reported incidence of DVT ranges from 15% to 29% for general or gynecologic surgery in the absence of DVT prophylaxis [4, 10, 11]. PE is one of the most common causes of nonsurgical death in patients following surgery, and the frequency of PE has been reported to be between 0.5% and 1.6% [10,11]. Although there is a paucity of randomized control trials (RCTs) that address this issue in digestive surgery, all patients undergoing digestive surgery have the potential to develop DVT and subsequently PE. The DVT risk in digestive patients undergoing an open pelvic surgery, including colo-rectal resection performed for a cancer and peritonitis, was estimated to be 22%–32% without prophylaxis [13, 14], suggesting that these results are similar to the rates of thromboembolic complications associated with other general surgeries.

In recent years, numerous digestive surgical procedures have been laparoscopically or robotically performed. These procedures offer distinct advantages over conventional open surgery, including decreased pain, quicker convalescence, shorter hospital stay, better cosmesis, and a comparable therapeutic efficacy and acceptable efficiency. Unfortunately, there are no randomized prospective studies that address the development of DVT in laparoscopic surgery; however, several reports in the literature have retrospectively reviewed symptomatic DVT and PE occurrences in patients with prostate cancer undergoing laparoscopic or robot-assisted laparoscopic radical prostatectomy. In one study, there were 31 patients (0.5%) who developed symptomatic DVT including 9 patients (0.2%) with PE among 5951 patients and two patients died of PE [7]. Another study involving a retrospective analysis of patients undergoing laparoscopic or robot-assisted laparoscopic radical prostatectomy found only 2 cases (0.3%) of DVT among 680 patients [15]. In 482 laparoscopic nephrectomies conducted, one PE case (0.2%) was noted, although it is unclear whether any DVT prophylaxis treatments were included [6]. These reports suggest that the DVT risk in urologic laparoscopic surgery appears to be lower, but accurate DVT rates may be higher if screening imaging techniques are utilized rather than clinical observations.

Although increasing accumulating evidence demonstrates that DVT does not occur more often with laparoscopic surgery than with open procedures, the abdominal insufflation used during laparoscopic procedures has been proposed to cause serum hypercoagulability of varying degrees and VTE secondary to venous stasis with a concomitant higher risk of DVT and PE [8, 9]. DVT complications are associated with long-term suffering and postthrombotic syndromes that include pain, heaviness, swelling, varicose veins, leg ulcers, and significant comorbidity, long-term medication, and death in some cases. Although the rates of such complications are low, DVT prophylaxis should be attempted by all conceivable means in all patients undergoing urologic laparoscopic surgical procedures whenever possible.

In this study, both enoxaparin (4000 UI once daily for 10 days) and IPC treatment using pneumatic compressive stockings were administered in all patients. In general, therapeutic measures for thromboprophylaxis provide two options, nonpharmacologic physiotherapy that includes early ambulation, graduated compression stockings, and IPS or pharmacologic agents that include low-dose unfractionated heparin (LDUH) and LMWH. Considerable controversy exists regarding the significance of pharmacologic prevention against VTE during laparoscopic surgery because of the low VTE incidence, risk of hemorrhagic complications associated with such agents, and the cost-effectiveness of prophylaxis. The American Urological Association (AUA) recommends the use of IPC devices before laparoscopic surgery or robotically assisted urologic procedures in all patients. In addition, noting the lack of large RCTs, high-risk groups may require the use of LDUH or LMWH before, during, or after surgical procedures [16]. In contrast, Van Hemelrijck et al. concluded that both physiotherapeutic and pharmacological prophylaxis should be used after all major surgeries including laparoscopic surgery for abdominal cancer [17]. Furthermore, in guidelines published by the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES), the use of LMWH is recommended as an option for all types of laparoscopic surgery [18]. In addition, a recent report on efficacy of enoxaparin in patients undergoing abdominal or pelvic cancer surgery has indicated that enoxaparin can offer patients an advantage over using IPC alone for VTE prevention [19].

The use of pharmacologic agents may increase the incidence of hemorrhagic complications during surgery. Moreover, the occurrence of spinal epidural hematoma when using enoxaparin with epidural or spinal anesthesia was reported [20], but enoxaparin has a reduced risk of heparin-induced thrombocytopenia and hemorrhagic complications, severe bleeding, or wound hematomas compared with LDUH in large RCTs [21, 22]. Because our data from hematological examinations and clinical observations indicate that coagulability was not excessively affected by enoxaparin, we propose that this treatment is safe and efficacious without the need for laboratory monitoring of patients when appropriately used. Although our results do not support enoxaparin administration for all patients undergoing a digestive laparoscopic surgery, an initial enoxaparin administration before surgery or immediately after surgery might be considered for high-risk patients.

Table 1: Disease and surgical procedure

DISEASE AND PROCEDURE

EFFECTIF (%)

Emergency surgery

96 (57)

          Acute peritonitis

28 (16)

          Acute cholelithiasis

66 (39)

          Acute cholangitis

2 (1)

Elective surgery

73 (43)

         Hernia

56 (33)

         Colorectal cancer or IBD

8 (4.7)

         Colorectal polyposis

4 (2.3)

         Gastrooesophagal reflux

2 (1.1)

         Stenosing duodenal ulcer

3 (1.7)

IBD: Inflammatory bowel disease

Table 2: Risk factors of venous thromboembolism

RISK FACTORS OF VTE

EFFECTIF (%)

Personal history of VTE or EP

2 (1. 1)

Familiary history of VTE or EP

6 (3.5)

Age > 40 years

128 (75.7)

Oral contraception

25 (14.7)

Obesity

35 (20)

Bed rest > 4 days

25 (14.7)

Active cancer

16 (9.4)

Cerebral infarction

2 (1.1)

Severe acute infection

13 (7.6)

VTE: Venous thromboembolism

EP: Embolism pulmonary

 

CONCLUSION

In the present study, we evaluated the validity of chemoprophylaxis using enoxaparin for the prevention of VTE in patients undergoing digestive laparoscopic surgery. With the exception of economic limitations, this approach might be a valuable tool for prevention of perioperative thromboembolic complications. To select the most adequate type of DVT prophylaxis in patients undergoing digestive laparoscopic surgery, the establishment of an appropriate prophylactic regimen and patient risk stratification is required.

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