Obstructive jaundice and coagulation disturbances

Pavlidis ET, Pavlidis TE. Pathophysiological consequences of obstructive jaundice and perioperative management. Hepatobiliary Pancreat Dis Int. 2018 Feb;17(1):17-21.

Full-text for Emory users.

“Proper management includes full replacement of water and electrolyte deficiency, prophylactic antibiotics, lactulose, vitamin K and fresh frozen plasma, albumin and dopamine. The preoperative biliary drainage has not been indicated in overall, but only in a few selected cases.”

“The coagulation disorders and the resulting hemostasis impairment have been attributed to the complement activation by endotoxin as well as to the reduced synthesis of prothrombin (factor II) in the liver and the other vitamin K depended coagulation factors i.e. VII, IX, X and proteins C, S, Z. The absence of bile salts in the gut prevents the absorption of vitamin K, which is a fat-soluble vitamin. In addition, the endogenous microbial flora produces small amounts of vitamin K. Subsequently the reduced vitamin K absorption results in its deficiency. The latter predisposes to bleeding diathesis, despite the normal laboratory indices such as prothrombin time (PTT) and international normalized ratio (INR). Likewise, the other fat-soluble vitamin D and lipids absorption is diminished resulting in their deficiency and calcium reduction.” (Pavlidis, et al., p. 19.)

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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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Perioperative Management of Biologic and Immunosuppressive Medications in Patients With Crohn’s Disease

Lightner AL. Perioperative Management of Biologic and Immunosuppressive
Medications in Patients With Crohn’s Disease. Dis Colon Rectum. 2018 Apr;61(4): 428-431.

EVALUATION AND TREATMENT ALGORITHMS

Algorithm 1

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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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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.

Intraoperative cardiac arrest: Resuscitation and Management

One discussion this week included intraoperative cardiac arrest.


Reference: Moitra VK, et al. Cardiac arrest in the operating room: resuscitation and management for the anesthesiologist: part 1. Anesthesia & Analgesia. 2018 Mar;126(3):876-888. doi: 10.1213/ANE.0000000000002596.

Summary: Cardiac arrest in the operating room and procedural areas has a different spectrum of causes (ie, hypovolemia, gas embolism, and hyperkalemia), and rapid and appropriate evaluation and management of these causes require modification of traditional cardiac arrest algorithms. There is a small but growing body of literature describing the incidence, causes, treatments, and outcomes of circulatory crisis and perioperative cardiac arrest. These events are almost always witnessed, frequently known, and involve rescuer providers with knowledge of the patient and their procedure.

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D1 vs D2 resection for gastric cancer

One discussion this week included a trial out of Denmark comparing D1 and D2 lymph-node dissection for gastric cancer.

Reference: Bonenkamp JJ, et al. Extended lymph-node dissection for gastric cancer. NEJM. 1999 Mar 25;340(12):908-914.

Summary: Curative resection is the treatment of choice for gastric cancer, but it is unclear whether this operation should include an extended (D2) lymph-node dissection or a limited (D1) dissection. The authors conducted a randomized trial in 80 Dutch hospitals in which they compared D1 with D2 lymph-node dissection for gastric cancer in terms of morbidity, postoperative mortality, long-term survival, and cumulative risk of relapse after surgery.

Between August 1989 and July 1993, 996 patients were enrolled. Of these, 711 underwent randomly assigned treatment (D1 = 380, D2 = 331) and 285 received palliative treatment.

General findings:

  • Complications: 43% in D2, 25% in D1
  • Postoperative deaths: 10% in D2, 4% in D1
  • Length of stay: 16 median days in D2, 14 days in D1
  • 5-year survival rates: 47% in D2, 45% in D1

 

d1 v d2

One of the arguments for D2 dissection is its ability to reduce rates of local recurrence, thereby increasing the quality of life. The distressing finding of local recurrence, usually in a terminal phase of the disease, often leads to second operations to restore gastrointestinal continuity. In this trial, there was a tendency toward a reduced cumulative risk of relapse after D2 dissection, but the rate of relapse remained high and the difference from D1 dissection was not significant. A subgroup analysis indicated a significant or marginally significant difference for patients with disease in UICC stages II and IIIA, but this difference was attributable largely to stage migration.

The MAGIC Trial: Does perioperative ECF improve outcomes for gastric cancer patients?

One discussion this week included the Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) Trial. [Current Controlled Trials number: ISRCTN93793971.]

Reference: Cunningham D, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. NEJM. 2006 Jul 6;355(1):11-20.

Summary: A regimen of epirubicin, cisplatin, and infused fluorouracil (ECF) improves survival among patients with incurable locally advanced or metastatic gastric adenocarcinoma. The MAGIC Trial assessed whether the addition of a perioperative regimen of ECF to surgery improves outcomes among patients with potentially curable gastric cancer.

METHODS: We randomly assigned patients with resectable adenocarcinoma of the stomach, esophagogastric junction, or lower esophagus to either perioperative  chemotherapy and surgery (250 patients) or surgery alone (253 patients). Chemotherapy consisted of three preoperative and three postoperative cycles of intravenous epirubicin (50 mg per square meter of body-surface area) and cisplatin (60 mg per square meter) on day 1, and a continuous intravenous infusion of fluorouracil (200 mg per square meter per day) for 21 days. The primary end point was overall survival.

CONCLUSIONS: In patients with operable gastric or lower esophageal adenocarcinomas, a perioperative regimen of ECF decreased tumor size and stage and significantly improved progression-free and overall survival.

MAGIC

(p.16)

Additional Reading: Cunningham D, et al. Perio-operative chemoterhapy with or without bevacizumab in operable oesophagogastric adenocarcinoma (UK Medical Research Council ST03): primary analysis results of a multicentre, open-label, randomised phase 2-3 trial. Lancet Oncology. 2017 Mar;18(3):357-370.  doi: 10.1016/S1470-2045(17)30043-8.

[ClinicalTrials.gov, number NCT00450203.]