Study design
This was a prospective, non-consecutive cohort study conducted from June 2011 to February 2013. This study was approved by the Human Subjects Internal Review Board at Lifespan, Inc., and Rhode Island Hospital. Written informed consent was obtained by each subject's parent or legal guardian.
Setting and participants
The Bedside Ultrasound to Detect Dehydration in Youth (BUDDY) study was conducted in a busy, tertiary care pediatric emergency department (PED) at Hasbro Children's Hospital in Providence, Rhode Island, with an annual census of approximately 50,000 PED visits.
Subjects were enrolled as a convenience sample based on investigator availability. Investigators were available to enroll patients Monday through Friday, from 9 a.m. until 5 p.m., excluding holidays. All children less than or equal to 18 years of age presenting with a chief complaint of vomiting and/or diarrhea, or suspicion of dehydration by an attending pediatric emergency physician were eligible for enrollment. Eligible patients whose initial order sets included plans for intravenous fluids were approached for study consent, and those only receiving oral fluids were not included in the study. Exclusions criteria included positive pressure ventilation, significant traumatic injury, large volume fluid administration prior to enrollment, surgical abdomen, and known congenital cardiac disease or pulmonary hypertension. Only English speaking patients were enrolled.
Patient assessment
Enrollment, weights, and ultrasound exams of the subjects were conducted by trained research assistants and resident physicians in Emergency Medicine. All study staff participated in a brief training by the principle study investigator (SS) including technique for patient weights using infant and child scales and ultrasound technique for the two ultrasound measures recorded. Ultrasound training consisted of both a lecture (30 min) and hands-on practice with proctored exams (1 to 5).
Calculation of percentage of dehydration
Research assistants weighed each child prior to intravenous fluid administration and again at the completion of ED resuscitation. Children admitted to the inpatient service for further hydration were weighed again prior to hospital discharge. All weights were performed without the child wearing clothes and with the same calibrated study scale (Seca Iena 354 for infants and Seca 813 Robusta for children able to stand, Seca, Handover, MD). The final weight was recorded as the weight upon discharge from the ED or from the hospital for admitted patients. The initial weight was that obtained upon enrollment. The percent dehydration was determined using the following formula: (final weight – initial weight)/final weight × 100%. Subjects with a percentage weight change of 5% or greater were considered to be significantly dehydrated. Significant dehydration was defined as moderate (5 to 10%) and severe (>10%) dehydration combined as previously described in the pediatric literature [5],[10],[15],[17].
Ultrasound protocol
Bedside ultrasound was performed by a study investigator using a Sonosite M-Turbo ultrasound machine (Bothell, WA) and curved footprint C-60 abdominal probe or a phased array P21 probe at the time of enrollment (beginning of the ED visit). There were four sonographer investigators participating in the study. Investigators performing the ultrasound were aware of the inclusion criteria but blinded to the treating clinician's impression of the degree of dehydration. Treating clinicians were blinded to the ultrasound results. The two ultrasound techniques were performed with subjects in the supine position with measurements obtained in B mode (see Figure 1).
For the IVC/Ao ratio using a cross section of both vessels for measurements, the transducer was placed over the anterior abdomen in the axial or transverse plane just below the level of the xyphoid bone. The aorta and IVC were visualized in cross section, and a 6-s video clip in addition to measured still images were recorded for later review. Diameters of the Ao and IVC were both measured using calipers in their maximal size, during systole for the aorta, and expiration for the IVC, from anterior to posterior (see Figure 2).
For the long axis view of the IVC to assess collapsibility with inspiration, one of two techniques was used. The probe was either placed midline in the sagittal plane with the marker towards the patient's head or on the patient's right side, coronal plane, and mid-axillary line with the marker towards the head. The probe position was chosen based on where the study investigator felt the best view could be obtained using the two techniques previously described in the literature [22]-[25]. A 6-s video clip was recorded, and then still images during inspiration and expiration were obtained. Still images of the maximum and minimum diameter of the IVC were measured, 2 cm from the right atrium-caval junction at the diaphragm or near the level of the entry of the hepatic veins as described previously in the literature (see Figure 3) [26]-[28].
Data collection
After enrollment, the treating pediatric emergency medicine attending physician, who had examined the patient and was blind to the ultrasound findings, recorded their clinical gestalt for percent dehydration on a data sheet with a 1 to 10 scale of gestalt of dehydration. Afterward, a research assistant documented the patient's vitals, weight, clinical score, and volume of fluid administered.
Outcomes
Our primary outcomes were to assess the accuracy of ultrasound measurements of the IVC/Ao ratio and the collapsibility index of the IVC, for prediction of significant dehydration in children relative to the criterion standard of percent weight change. Our secondary outcome was to assess the accuracy of physician gestalt compared to the same criterion standard.
Data analysis
First, we calculated basic population demographics using descriptive statistics. We then constructed receiver operating characteristic (ROC) curves to evaluate the accuracy of the IVC/Ao ratio, collapsibility index of the IVC, and physician gestalt compared to our criterion standard. We also calculated the sensitivity, specificity, likelihood ratio positive (LR+), and likelihood ratio negative (LR−) for both ultrasound measurements and physician gestalt. We calculated these test characteristics using the traditionally used cutoff points of IVC/Ao ratio (0.8) and collapsibility index of 50%. In addition, we calculated test characteristics for a cutoff point of IVC collapsibility index of 80% or greater because it was the best cutoff point obtained on the ROC curve to rule out dehydration and, therefore, the most clinically relevant.
To determine inter-rater reliability between ultrasound observers, an ultrasound fellowship trained investigator, blinded to the study results and prior measurements, reviewed the ultrasound clips of a selected random subgroup of 30 patients, and re-measured the IVC/Ao ratio, as well as the maximum and minimum diameter of the long axis view of the IVC during the normal breath cycle. Intra-class correlation coefficients were calculated to determine the degree of reliability for these measurements.
Statistical analyses were performed using Stata version 11.0 (StataCorp LP, College Station, TX).
Sample size
The sample size was originally calculated based on the IVC/Ao ultrasound component of the study. Using standard algorithms from the literature, an area under the ROC curve (AUC) of 0.756 for the performance of IVC ultrasound as a predictor of dehydration based on data previously obtained, a type I error rate of 0.05, a type II error rate of 0.20, and the proportion of children with significant (>5%) dehydration, in prior studies conducted in North American hospitals, we determined we would need to enroll at least 112 children to be sure that the 95% confidence intervals for our ROC curve did not cross the reference line (or null hypothesis). Significant dehydration was defined as moderate (5 to 10%) and severe (>10%) dehydration combined as previously described in the literature [5],[10],[15],[17].