Guidelines for the perioperative management of anticoagulants

One discussion this week focused on the perioperative management of NOACs.


Reference:  DynaMed Plus [Internet]. Ipswich (MA): EBSCO Information Services. 1995 -. Record No. 227537, Periprocedural management of patients on long-term anticoagulation; [updated 2018 Oct 10, cited 2018 Oct 12; [about 26 screens]. Emory login required.

Summary: The information below is from DynaMed Plus (2018). To view full information on the topic, click on the citation above.

Vitamin K antagonists in patients undergoing major surgery or procedures

  • Consider continuing vitamin K antagonist (VKA) therapy in patients who require minor dental procedures, minor dermatological procedures, or cataract surgery.
  • In those having a minor dental procedure, consider coadministering an oral hemostatic agent or stopping the VKA 2 to 3 days before the procedure.
  • In those undergoing implantation of a pacemaker or an implantable cardioverter device, consider continuing VKA therapy.
  • In those having a major surgery or procedure, stop VKA therapy 5 days before surgery.
  • Resume VKA therapy 12-24 hours after surgery when there is adequate hemostasis.

Bridging therapy in patients undergoing major surgery or procedures

  • If at low risk for thrombosis, consider omitting bridging therapy.
  • If at moderate risk for thrombosis, assess individual patient- and surgery-related factors when considering bridging therapy.
  • If at high risk for thrombosis consider bridging therapy with unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH).
  • For those receiving bridging therapy with UFH, stop UFH 4-6 hours before surgery.
  • For those receiving bridging therapy with therapeutic-dose LMWH, stop LMWH 24 hours before surgery.
  • For those receiving bridging therapy with UFH or therapeutic-dose LMWH and undergoing non-high-bleeding-risk surgery, consider resuming heparin 24 hours after surgery.
  • For those receiving bridging therapy with UFH or therapeutic-dose LMWH and undergoing high-bleeding-risk surgery, consider resuming heparin 48-72 hours after surgery.

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Signet-ring cell carcinoma: a look at the rare colorectal cancer

A discussion this week included signet ring cell carcinoma.


Reference: Nitsche U, et al. Mucinous and signet-ring cell colorectal cancers differ from classical adenocarcinomas in tumor biology and prognosis. Annals of Surgery. 2013 Nov;258(5):775-782; discussion 782-783. doi:10.1097/SLA.0b013e3182a69f7e

Additional Reading: Korphaisarn K, et al. Signet ring cell colorectal cancer: genomic insights into a rare subpopulation of colorectal adenocarcinoma. British Journal of Cancer. 2019 Sep;121(6):505-510. doi:10.1038/s41416-019-0548-9

Summary: In a study analyzing clinical, histopathological, and survival data of 3479 patients undergoing surgery for primary colorectal cancer between 1982 and 2012, Nitsche et al (2013) compared the characteristics of classical adenocarcinomas (AC) to the less common mucinous adenocarcinomas (MAC) and to the rare signet-ring cell carcinomas (SC).

SC

Approximately 10% of all colorectal cancers are MAC, and about 1% are SC. Because of their relatively rare occurrence, in particular, the evaluation of the clinical impact of SC is difficult. However, compared with AC, both MAC and SC have been shown to be associated with young age, advanced tumor stage, accumulation in female patients, and distinct molecular patterns, such as microsatellite instability and activating mutations of the BRAF gene. Although ambiguous, recent data and meta-analyses suggest that the
histological subtype MAC may be associated with worse outcome compared with AC. Poor prognosis of SC is more evident, mainly due to high rates of synchronous and metachronous distant organ metastasis associated with this histological subtype.

In describing SC, the authors state: “SC have been described as being positive for intestinal trefoil factor and MUC2, 2 peptides that are usually produced only by goblet cells. Thus, SC could arise from different cells of origin than AC. Although they can be localized in the colorectum, SC may be genetically more related to signet-ring cell cancers of other organs (eg, gastric cancer) than to AC or MAC of the colorectum. The
absence of E-cadherin/β-catenin and amplification of Bcl-2 are features typically shared with signet-ring cell cancer of the stomach but not with classical colorectal adenocarcinomas” (p.781).

The authors conclude that patients with MAC and SC could profit from closer follow-up or even intensified adjuvant therapy because of their high rates of local and distant recurrence. The biological behavior of SC differs in specific, and these patients require special awareness, despite the relatively rare prevalence.

AAA repair: retroperitoneal vs transperitoneal approach

One discussion this week included transperitoneal vs retroperitoneal  approach following AAA repair.


Reference: Buck DB, et al. Transperitoneal vs retroperitoneal approach for open abdominal aortic aneurysm repair in the targeted vascular NSQIP. Journal of Vascular Surgery. 2016 Sept;64(3):585-591. doi:10/1016/j.jvs.2016.01.055.

Summary: This study aims to identify the demographic and anatomical differences between patients currently selected for elective transperitoneal versus retroperitoneal AAA repair and to assess differences in intra-operative details, and perioperative mortality and complications.

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The PAUSE study: Safety of perioperative DOAC management in patients with atrial fibrillation

A discussion during a previous conference included the perioperative management of patients with atrial fibrillation receiving a direct oral anticoagulant (DOAC).


Reference: Douketis JD, et al. Perioperative management of patients with atrial fibrillation receiving a direct oral anticoagulant. JAMA Internal Medicine. 2019 Aug 5; doi:10/1001/jamainternmed.2019.2431

Summary: Each year, 1 in 6 patients with AF, or an estimated 6 million patients worldwide, will require perioperative anticoagulant management. When DOAC regimens became available for clinical use in AF, starting in 2010, no studies had been conducted to inform the timing of perioperative DOAC therapy interruption and resumption, whether heparin bridging should be given, and whether preoperative coagulation function testing was needed. Uncertainty about the perioperative management of DOACs may be associated with unsubstantiated practices and increased harm to patients.

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Open vs endovascular revascularization for ALI: a review of major trials

One discussion this week involved open surgical versus endovascular revascularization for acute limb ischemia (ALI).

Reference: Wang JC, Kim AH, Kashyap VS. Open surgical or endovascular revascularization for acute limb ischemia. Journal of Vascular Surgery. 2016 Jan;63(1):270-278. doi:10/1016/j.jvs.2015.09.055.

Summary: Peripheral arterial disease affects approximately 10 million Americans. It can lead to lower extremity ischemic rest pain or tissue loss (Rutherford classification 4 to 6, or Fontaine classification III and IV). Acute limb ischemia (ALI) is defined as the presence of symptoms within 2 weeks of onset. ALI pathogenesis includes vascular stenoses with subsequent in situ thrombosis or thromboembolism from a cardiac or aortoiliac source. Stenotic lesions may indicate untreated comorbidities (eg, hypertension, hypercholesterolemia, diabetes, or tobacco use), whereas thromboembolisms implicate undiagnosed cardiac arrhythmias, myocardial infarction (MI), or mural thrombus. Limb loss risk due to ALI can be as high as 40% with an attendant mortality rate of 15% to 20% (p.270).

Limb salvage (LS) revascularization is traditionally achieved with emergent surgical thromboembolectomy or bypass. Catheter-based technologic advancements have afforded a wide array of endovascular therapy (ET) amenable for treating ALI, including catheter-directed thrombolysis (CDT), pharmacomechanical thrombolysis (PMT), angioplasty, and stenting.

For this review, a systematic literature review using MEDLINE (1990-
2014) was performed with querying keywords acute limb ischemia, acute occlusion, peripheral arteries, thrombectomy, thrombolysis, and complications. Clinical trials, registry reports, open vs endovascular arterial revascularization, and review articles were included. Attention was given to revascularization techniques, short- and long-term patency, LS rates, amputation-free survival (AFS), overall survival (OS), and complications. Four RCTs and 5 other study types were analyzed.

RCTs1

 

RCTs2

 

CONCLUSION: ALI remains a morbid condition with high risk for limb loss and death. Based on the current evidence, ET is effective for LS and safer in the short term than urgent open revascularization in the studied patients. Still, individual patient factors need to be carefully considered for further generalization. ET and surgery are complementary rather than competing strategies for treating ALI. Further good-quality clinical trial data are required to define longer term outcomes.

The benefit of urinary alkalinization and mannitol in the treatment of rhabdomyolysis

One discussion this week included the benefits of urinary alkalinization and mannitol in treating rhabdomyolysis (RM).


Reference: Bada A, Smith N, and Surgical Critical Care Guidelines Committee. Rhabdomyolysis: Prevention and Treatment. SurgicalCritical Care.net. 2018, Jul 24.

Summary: RM is the dissolution muscle and release of potentially toxic intracellular components into the systemic circulation. RM has the potential to cause myoglobinuric ARF in 10-15% of such patients. Overall, 10-15% of ARF in the United States is from RM.

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True or False: Atelectasis as cause of postoperative fever.

One discussion this week included atelectasis as a potential cause of postoperative fever.


Reference: Crompton JG, Crompton PD, Matzinger P. Does atelectasis cause fever after surgery? Putting a damper on dogma. JAMA Surgery. 2019 Mar 6:154(5):375-376. doi:10.1001/jamasurg.2018.5645.

Summary: Fever and atelectasis are common after surgery, and in the absence of infectious causative mechanisms, atelectasis is commonly thought to be a cause of fever. The therapeutic implication of atelectasis as a putative cause of postoperative fever has been the widespread adoption of incentive spirometry to reduce atelectasis.

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Upper GI bleeding: CTA prior to flouroscopic angiography?

A discussion this week included a diagnostic CTA prior to flourscopic angiography.


Reference: Wells ML, et al. CT for evaluation of acute gastrointestinal bleeding. RadioGraphics. 2018 Jul-Aug;38(4):1089-1107. doi:10.1148/rg.2018170138

Summary: “Teaching point: CT angiography is gaining popularity for use in emergent evaluations of acute GI bleeding. It has potential for use in the first-line evaluation of acute LGIB and the evaluation of UGIB after failed or nondiagnostic endoscopy.”

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Balanced crystalloids vs saline in adult non-ICU patients

One discussion this week included the question of balanced crystalloids vs saline in ICU and non-ICU patients.

Reference: Self WH, et al. Balanced crystalloids versus saline in noncritically ill adults. NEJM. 2018 Mar 1; 378:819-828. doi:10.1056/NEJMoa1711586

(Funded by the Vanderbilt Institute for Clinical and Translational Research and others; SALT-ED ClinicalTrials.gov number, NCT02614040.)

Summary: METHODS: This was a single-center, pragmatic, multiple-crossover trial comparing balanced crystalloids (lactated Ringer’s solution or Plasma-Lyte A) with saline among adults who were treated with intravenous crystalloids in the emergency department and were subsequently hospitalized outside an ICU. The type of crystalloid that was administered in the emergency department was assigned to each patient on the basis of calendar month, with the entire emergency department crossing over between balanced crystalloids and salinemonthly during the 16-month trial. The primary outcome was hospital-free days (days alive after discharge before day 28). Secondary outcomes included major adverse kidney events within 30 days – a composite of death from any cause, new renal-replacement therapy, or persistent renal dysfunction (defined as an elevation of the creatinine level to ≥200% of baseline) – all censored at hospital discharge or 30 days, whichever occurred first.

RESULTS: A total of 13,347 patients were enrolled, with a median crystalloid volume administered in the emergency department of 1079 ml and 88.3% of the patients exclusively receiving the assigned crystalloid. The number of hospital-free days did not differ between the balanced-crystalloids and saline groups (median, 25 days in each group; adjusted odds ratio with balanced crystalloids, 0.98; 95% confidence interval [CI], 0.92 to 1.04; P=0.41). Balanced crystalloids resulted in a lower incidence of major adverse kidney events within 30 days than saline (4.7% vs. 5.6%; adjusted odds ratio, 0.82; 95% CI, 0.70 to 0.95; P=0.01).

The authors note that a strength of this trial was high adherence to the assigned crystalloid group. Use of an unblinded, pragmatic design in a learning health care system facilitated incorporation of the trial into routine practice, allowing the assigned crystalloid to be systematically used for early fluid resuscitation immediately after arrival in the emergency department.

CONCLUSION: Among noncritically ill adults treated with intravenous fluids in the emergency department, there was no difference in hospital-free days between treatment with balanced crystalloids and treatment with saline.

Balanced crystalloids vs saline in adult ICU patients

One discussion this week included the question of balanced crystalloids vs saline in ICU and non-ICU patients.


Reference: Semler MW, et al. Balanced crystalloids versus saline in critically ill adults. NEJM. 2018 Mar 1;378:829-839. doi:10.1056/NEJMoa1711584

Summary: Although both saline and balanced crystalloids have been administered to patients in clinical practice for decades, few trials have addressed the effects of crystalloid composition on clinical outcomes.

The authors conducted an unblinded, cluster-randomized, multiple-crossover trial in which the use of balanced crystalloids was compared with saline for intravenous fluid administration among critically ill adults admitted to five ICUs at Vanderbilt University Medical Center between June 1, 2015, and April 30, 2017. A total of 15,802 patients were enrolled. The median age was 58, and 57.6% of patients were men.

The primary outcome was the proportion of patients who met one or more criteria for a major adverse kidney event within 30 days — the composite of death, new receipt of renal-replacement therapy, or persistent renal dysfunction (defined as a final inpatient creatinine value ≥200% of the baseline value) — all censored at hospital discharge or 30 days after enrollment, whichever came first.

Among the 7942 patients in the balanced-crystalloids group, 1139 (14.3%) had a major adverse kidney event, as compared with 1211 of 7860 patients (15.4%) in the saline group (marginal odds ratio, 0.91; 95% confidence interval [CI], 0.84 to 0.99; conditional odds ratio, 0.90; 95% CI, 0.82 to 0.99; P=0.04). In-hospital mortality at 30 days was 10.3% in the balanced-crystalloids group and 11.1% in the saline group (P=0.06). The incidence of new renal-replacement therapy was 2.5% and 2.9%, respectively (P=0.08), and the incidence of persistent renal dysfunction was 6.4% and 6.6%, respectively (P=0.60).

In this trial of critically ill adults, the intravenous administration of balanced crystalloids rather than saline had a favorable effect on the composite outcome of death, new renal-replacement therapy, or persistent renal dysfunction.

Additional Reading: Hammond DA, et al. Balanced crystalloids versus saline in critically ill adults: a systematic review and meta-analysis. Annals of Pharmacotherapy. 2019 Jul 31:1060028019866420. doi: 10.1177/1060028019866420.