OUTPATIENT LIVER BIOPSY IN CHILDREN: A Medical Position Statement of the North American Society for Pediatric Gastroenterology and Nutrition

Victor L. Fox, MD, Children's Hospital, Harvard Medical School
Mitchell B. Cohen, MD, Children's Hospital, University of Cincinnati
Peter F. Whitington, MD, Wyler Children's Hospital, University of Chicago
Richard B. Colletti, MD, Department of Pediatrics, University of Vermont College of Medicine

[This Medical Position Statement was published in the Journal of Pediatric Gastroenterology and Nutrition, October 1996, and is edited for electronic communication by R. Colletti.]

INTRODUCTION

The North American Society for Pediatric Gastroenterology and Nutrition (NASPGN) recognizes the need to develop a medical position statement on percutaneous liver biopsy in infants and children, in order to promote optimal patient care, to foster learning and to guide practitioners, as well as to facilitate peer and other review of clinical practices. The changing healthcare environment encourages cost containment by placing greater emphasis on outpatient medical services. The outcome of diagnostic and therapeutic procedures has come under increasing scrutiny to determine which procedures may be safely and successfully conducted on an outpatient basis. Professional review organizations and medical insurance providers frequently limit reimbursement approval for percutaneous liver biopsy to an outpatient status for adult patients. The basis for this decision is published outcome data dating from 1978 to present which demonstrate that such an approach is safe in carefully selected adult patients.1-4 Guidelines for outpatient percutaneous liver biopsy (OLB) were formulated by the Patient Care Committee of the American Gastroenterological Association and published in 1989.5 These guidelines mention "the very young" as potentially higher risk patients who might warrant exclusion from this OLB. However, no detailed recommendations regarding appropriate selection or exclusion criteria for children were included. Pediatric gastroenterologists have continued to make decisions about percutaneous liver biopsy, including whether to perform OLB, based upon limited published data and personal or anecdotal experience.

REPORTED EXPERIENCE

Early English language reports of percutaneous liver biopsy in children involved investigation of liver histology during malnutrition. In 1945 there were no reported complications associated with 92 biopsies in 45 infants and children with pellagra.6 In 1949 there were no complications described in 89 biopsies in 29 children between 4 and 30.5 months of age suffering from "nutritional dystrophy".7 Subsequently, there have been 9 additional reports published from 1955 to 1993 that include a total of 2,024 biopsies in more than 1,700 children (Table).8-16 Other reports include very few patients or inadequate information about children within a larger adult patient series. Most studies gathered complication data retrospectively. The reported rates of major complications ranged from 0 to 4.5%. The incidence of post-biopsy hemorrhage requiring transfusion ranged from 0 to 2.8%. Other major complications in children, like in adults, have included pneumothorax, hemothorax, hemoperitoneum, subcapsular hematoma, bile leak, ascitic fluid leak, and pneumoscrotum.17 Three pediatric deaths have been reported.

A 1993 survey of 414 active members of the North American Society of Pediatric Gastroenterology and Nutrition (57% responding) indicated that a minority (28%) of respondents had experience with OLB in children when defined as post-biopsy monitoring for less than 8 hours (VL Fox, unpublished data). In the only detailed series of children undergoing OLB, no significant complications were reported after 184 biopsies in 104 patients.16 More than two-thirds of the biopsies were performed in patients who were recipients of a liver transplant. In the same study, 5 (1%) of 521 biopsies performed on inpatients resulted in significant hemorrhage.

The results of OLB in series of mixed pediatric and adult patients have been reported. In a series of 107 patients between 8 and 73 years of age, one patient suffered major hemorrhage requiring surgical control.1 In another series of 829 patients 11 to 84 years of age, 44 (5.3%) required hospitalization for unplanned observation or treatment and 31 patients (3.6%) suffered major complications.2 No specific information was provided in these studies about the number of children involved or their outcome relative to the adult subjects. The complication rate of OLB in adult patients is 2.7% (range, 0 to 3.6%) based on a cumulative total of 2,166 patients in 9 separate series.4 This may be compared with a complication rate of 0.28% (range 0.12 to 0.63%), and a mortality of 0.03% (range, 0 to 0.12%), among 189,085 adult patients undergoing inpatient liver biopsy reported in 6 separate studies.4 However, there have been no prospective studies comparing the relative risk of complication from percutaneous liver biopsy in inpatients and outpatients.

The major difference between OLB and inpatient liver biopsy is the shorter period of post-biopsy observation. The safety of OLB is determined by the relative frequency of complications occurring during and after the observation period. The guidelines of the American Gastroenterological Association for adult OLB recommend at least 6 hours for post-biopsy observation.5 Although most adults with significant complications manifest symptoms within 3 hours of the procedure, hypotension and death has occurred 9 hours after biopsy,18 and delayed bleeding has been described 15 days after biopsy.4,19 Since few complications have been reported, very little data are available regarding the onset of signs and symptoms of hemorrhage or other major complications following liver biopsy in children. In one study, all patients who required transfusion had either a decrease in hematocrit or changes in vital signs within four hours of the biopsy.15 In another study, all 5 patients with hemorrhage showed signs and symptoms within 2 hours of the biopsy.16 Although delayed-onset hypotension or death has not been mentioned in pediatric reports, late onset cardiovascular instability from hypovolemic shock remains a serious concern.

Data regarding OLB in adults cannot necessarily be extrapolated to the pediatric population. There are limited data upon which to base recommendations about outpatient liver biopsy in children, and data from studies in adult patients cannot be relied upon to predict outcome in children. Data from one institution may not be generalizable to others because of differences in the amount of experience, hospital resources, underlying liver diseases and family and community support. Published experience is likely to be more favorable than experience in general, since smaller centers and those with high rates of complications are less likely to publish their experience.

SHOCK IN INFANTS AND CHILDREN

Hemorrhage is the most important life-threatening complication following percutaneous liver biopsy, and the detection and treatment of hemorrhagic shock are critical to saving a patient's life in the event of this complication. Understanding the pathophysiology, diagnosis and treatment of hypovolemic shock in children is, therefore, important when considering OLB. The unique aspects of pediatric physiology and anatomy that place children at greater risk for hemorrhagic shock have recently been reviewed.20 Children have a relatively small total blood volume and lower hematocrit level than adults. The high ratio of body surface area to mass increases the risk for hypothermia and subsequent pulmonary hypertension, hypoxemia, and metabolic acidosis. Limited thermoregulation in infants due to inadequate subcutaneous fat and shivering mechanisms increases the risk for hypothermia and its consequences. Vital signs are age-related, and early detection requires familiarity with normal values. Tachycardia is the primary response to hypovolemia in children, and children receiving beta-blocking medications may be at greater risk for shock in the event of hemorrhage. In addition, gaining access to the peripheral venous system can be technically difficult.

The subtlety of early clinical signs of hypovolemic shock in infants and young children may contribute to delayed recognition and intervention in comparison with the management of adult patients. Children who are uncooperative or unable to accurately report symptoms are particularly difficult to assess for early signs of shock or other complications. Cardiovascular collapse may ensue more rapidly than anticipated. There are no laboratory tests which can be used conveniently to establish the diagnosis of shock or accurately assess acute blood volume loss. Irritability and tachycardia, both early signs of hypovolemia, may be easily overlooked or misinterpreted in an active child. Cool extremities and delayed capillary refill time (>2 seconds) indicate serious blood volume loss of 20 to 25%. These signs may also be overlooked if not deliberately sought. Hypotension is a late sign of critical blood volume loss approaching 40%. The problem of detection is compounded by difficulty in gaining quick access to peripheral veins for volume resuscitation of a small child or infant.

RECOMMENDATIONS

The following recommendations were prepared with the critique and endorsement of the Subcommittee on Endoscopy and Procedures, the approval of the Patient Care Committee, and the authorization of the Executive Council of NASPGN. These recommendations are subject to change based on periodic review of subsequent research.

Outpatient percutaneous liver biopsy in children and infants may be considered with the following understanding and provisions:

1. Because of potentially increased risks, and the greater difficulty of detecting and managing shock, infants and children requiring liver biopsy should not be compelled to have liver biopsy as outpatients. However, OLB may be considered if, in the judgement of the attending physician, certain conditions are met.

2. OLB should be performed in infants and children by a physician (or under the supervision of a physician) experienced in performing this procedure in pediatric patients, only in facilities that are well-equipped to provide pediatric care.

Liver biopsies in infants and children should only be performed in settings that afford adequate observation and support to patients. Such a facility includes the following: (a) it is part of or immediately adjacent to a pediatric inpatient facility to which the patient can be admitted without delay in the event of complications; (b) there are full laboratory and blood bank support; (c) there is nursing personnel experienced with pediatric patients undergoing liver biopsies to observe the patient closely post-biopsy; (d) there is adequate, modern equipment for constantly monitoring pulse, blood pressure, and oxygen saturation; (e) equipment for resuscitation is immediately available and maintained in proper working condition.

3. OLB should not be performed in patients with an unacceptably high risk for complication.

Patients with any of the following conditions may be at increased risk for either a complication, poor outcome or difficulty detecting hypovolemic shock following percutaneous liver biopsy: early infancy; advanced cirrhosis, ascites or coagulopathy; coexistent major organ system disease that would imperil the patient in the event of a complication (especially cardiac or pulmonary insufficiency); use of medications that may obscure a response to a complication (e.g., a beta receptor antagonist).

Patients with underlying conditions such as, but not limited to, active malignancy (particularly hematologic or metastatic to liver), AIDS, bone marrow transplantation and ischemic liver disease are at significantly higher risk for a complication or poor outcome following percutaneous liver biopsy, and generally are not considered candidates for OLB.

4. A protocol for OLB should be established before performing the procedure.

Although routine pre-biopsy testing varies among institutions, each institution should develop a consistent pre-biopsy protocol, including risk assessment. OLB protocols should generally be similar to protocols for inpatients. Screening laboratory studies should include but not be limited to a complete blood count, platelet count, and coagulation studies. Intravenous access is generally maintained for patients throughout the period of post-biopsy monitoring.

5. Patients must remain at the facility for at least 6 hours post-biopsy for frequent monitoring.

Any evidence of hemodynamic or other instability should result in continued hospitalization until significant complications have been excluded. Prior to release from the facility a repeat hematocrit should be obtained and the result noted for evidence of significant occult hemorrhage. Activity should be limited for the first 24 hours post-biopsy.

6. There should be a protocol for observation to detect complications that develop after the patient leaves the biopsy facility, and the patient and guardian should remain near enough to the facility to be able to return promptly.

The patient's family should continue to provide adequate observation for some time after the initial 6-8 hour period of post-biopsy observation. Children should not be considered for OLB unless they can be accompanied by a reliable guardian who will remain with them for a least 48 hours post-biopsy, can provide adequate supportive care and has immediate access to a telephone and transportation to the facility. In addition, in general for the first 24 hours post-biopsy the patient and guardian should remain within the vicinity of the facility so in the event of a complication the patient could return quickly to the facility (usually within approximately 30 minutes transportation time).

7. There should be a low threshold for utilizing the inpatient facility after OLB.

Post-biopsy hospitalization is advised if there is evidence of significant bleeding, respiratory distress, excessive pain, prolonged sedation, other organ puncture, bile leak or other complication.

REFERENCES

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