RESEARCH ARTICLE

Initial Validation of GRASP: A DifferentialDiagnoses Algorithm for Children With MedicalComplexity and an Unknown Source of PainBrenna L. Morse, PhD, RN-BC, NCSN, CNE,a Jean C. Solodiuk, PhD, RN,b Christine D. Greco, MD,b Sangeeta Mauskar, MD, MPH,b Julie Hauer, MDb,c

A B S T R A C T OBJECTIVES: Identifying the source of pain for children with medical complexity (MC) ischallenging. The purpose of this study was the initial validation of a tool to guide the medicalevaluation for identifying the source of pain in children with MC by using differential diagnoses.The tool is entitled Guidelines for Ruling Out and Assessing Source of Pain (GRASP).

METHODS: A mixed-methods approach that included expert review, focus groups, Web-basedsurveys, and a trial of the GRASP was used to determine validity as well as perceived clinical utility.

RESULTS: Focus groups were held with 26 inpatient and outpatient clinicians. Participantsconsistently responded in support of the GRASP. Participants advised several suggestions for toolorganization such as designing the tool as a flow diagram. Seven clinicians participated in Web-based surveys and made specific suggestions for making the GRASP more comprehensive. Sixparticipants trialed the GRASP for 14 children with MC and pain of unknown origin. Overall,participants found that the GRASP was a clinically effective tool for guiding medical evaluation.

CONCLUSIONS: These results provide preliminary evidence that the GRASP has content and facevalidity in evaluating the source of pain in children with MC. This tool can be used to systematicallyguide clinicians through a balanced approach to evaluation with a goal of determining the painsource, preventing harm, and relieving suffering without unnecessary tests.

aSolomont School ofNursing, University ofMassachusetts Lowell,Lowell, Massachusetts;

bBoston Children’sHospital, Boston,

Massachusetts; andcSeven Hills Pediatric

Center, Groton,Massachusetts

www.hospitalpediatrics.orgDOI:https://doi.org/10.1542/hpeds.2019-0322Copyright © 2020 by the American Academy of Pediatrics

Address correspondence to Brenna L. Morse, PhD, RN-BC, NCSN, CNE, Solomont School of Nursing, University of Massachusetts Lowell,113 Wilder St Suite 200, Lowell, MA 01824. E-mail: brenna_morse@uml.edu

HOSPITAL PEDIATRICS (ISSN Numbers: Print, 2154-1663; Online, 2154-1671).

FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.

FUNDING: Supported by the University of Massachusetts Lowell Internal Seed grant.

POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

Dr Morse conceptualized and designed the study, supervised data collection, collected data, conducted analyses, and drafted the initialmanuscript; Dr Solodiuk conceptualized and designed the study, designed the instrument, coordinated data collection, collected data,and reviewed and revised the initial manuscript; Drs Greco and Hauer aided in instrument design and critically reviewed themanuscript; Dr Mauskar aided in instrument design, coordinated data collection, collected data, and critically reviewed the manuscript;and all authors approved the final manuscript as submitted.

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Identifying the source of pain in a childwith medical complexity (MC) is oftenchallenging because the child cannotalways localize pain or provide detailsof their experience. Because self-reportis not possible for many children withMC, providers depend on parents and/orcaregivers to provide a comprehensivehistory to guide the diagnostic evaluation.Children with MC have been describedand, for the purposes of this article,are defined as having a “congenital oracquired multisystem disease, a severeneurologic condition with markedfunctional impairment, and/or technologydependence for activities of daily living.”1

Throughout this article, we chose toidentify the condition, not the child,with the acronym MC to writeefficiently.

Unfortunately, pain in children with MC iscommon.2–4 When compared with otherhospitalized children, children with MCtend to experience pain that is persistentand severe, which may be a resultof underlying disease processes,comorbidities, and difficulties in painassessment.2 Children with MC mayexperience both acute pain from fractures,otitis media, and pneumonia5 and chronicpain from spasticity or neuropathic pain.6,7

Some children with MC exhibit painbehaviors that are not typically associatedwith pain such as changes in mental status,laughter, and other vocalizations.4,8,9 Painassessment tools validated for childrenwho cannot provide self-reports of painare effective for measuring the presenceand intensity of pain8,10,11; however, thesetools do not guide clinicians in identifyingthe source of pain. Adding to the challengeof identifying the source of pain for thesechildren is a prevailing thought amongsome clinicians that children with MC feelor experience less or even no pain.12 Thechallenges surrounding pain assessmentin children with MC13–15 may contributeto lengthy and sometimes unnecessarymedical workups16 and delays in identifyingand addressing the source of pain.4,17

In turn, such delays may contribute toincreased morbidity for children withMC experiencing pain of unknownetiology.18,19

Although children with MC compose only5.2% of hospitalizations, they account for22% of hospital charges20 and 43% ofhospital deaths.21 Although commonpediatric conditions, such as otitis mediaand pneumonia, are typically treated in theoutpatient setting, the hospitalization ratefor these diagnoses is 6 times greater forchildren with MC than for neurotypicalchildren.22 Hospital readmission rates forchildren with MC are higher than for thegeneral pediatric population. In a caseseries of children with MC admitted to thehospital for an unidentified source of pain,children with MC stayed for nearly 2 weeksand required an average of 5 clinical imagesand 4 specialist consultations to identify asource of pain because of their MC.23 For allthese reasons, a thorough, efficient, andstandardized approach to the medicalevaluation to identify the source of pain isneeded for this vulnerable population.

The purpose of this study was the initialvalidation of a tool, the Guidelines for RulingOut and Assessing Source of Pain (GRASP),to direct the medical evaluation foridentifying the source of pain in childrenwith MC by using differential diagnoses.Differential diagnoses are a list of possiblecauses of a patient’s clinical findings usedto systematically consider and, at times,evaluate for possible causes beforeidentifying the final diagnosis. The specificaims included establishing (1) contentvalidity (with expert and professionaljudgment to ensure the tool adequatelyrepresents the pain evaluation process byusing differential diagnoses),24 (2) facevalidity (ensuring that nonexpertprofessionals determine that the toolappears to reflect the pain evaluationprocess),24 and (3) the perceived clinicalutility of the tool.

METHODS

A mixed-methods approach was used acrossstudy phases to establish face and contentvalidity as well as perceived clinical utility.Expert review, focus groups, Web-basedsurveys, and a test of the GRASP were usedas data collection methods. Institutionalreview board approval was obtained fromthe University of Massachusetts Lowell andBoston Children’s Hospital.

A retrospective medical chart review forchildren with MC admitted to a pediatrichospital for pain of unknown origin wasused to identify the need for a standardizedapproach to medical evaluation.23 Oneauthor (JCS) considered the literature andclinical experiences and developed the firstdraft of the GRASP. The GRASP is analgorithm that guides a standardizedapproach to medical evaluation with theinitial evaluation based on the severity ofthe child’s clinical condition and differentialdiagnoses organized by body system. TheGRASP (Fig 1) uses both prognostic andprobabilistic approaches to diagnosis. Aprognostic approach to diagnosingprioritizes clinical conditions, which, if leftundiagnosed and untreated, could be life-threatening. The first step in the GRASPsuggests tests to complete if the child withMC has pain behaviors of unknown etiologyand appears ill. Then the list of differentialdiagnoses takes a more probabilisticapproach to diagnosing by consideringdiagnoses that are likely to occur in thispopulation.

The tool was then reviewed and edited forwording and content on the basis of inputfrom local experts, including authors SM,JH, and CDG, and additional experts, whoare mentioned in the Acknowledgments. Thestudy team then revised the tool forreadability and organization.

Phase 1: Content and Face Validation

To determine content and face validity, 4 in-person focus groups with clinical experts onthe care of children with MC were held. Thespecific goals of these groups includedidentifying overall impressions of the GRASPand determining if the listed differentialdiagnoses were both comprehensive andnecessary to include in the tool.

Potential participants were identified asexperts in this field by both the patientpopulation that they care for and the yearsof experience caring for this population.Specifically, participants were determinedto be experts on the basis of years ofexperience in the area of pediatric pain,pediatric complex care, or completion ofspecialized training in pediatric pain and/orcomplex care. Experts were invited viae-mail to the focus group sessions held

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on-site at 2 pediatric hospitals. One hospitalwas a 404-bed pediatric medical center, andthe other was a 70-bed subacuterehabilitation center for children with MC.Both facilities offer comprehensive servicesfor children with MC. The focus groupinvitation e-mail included a copy of theGRASP for review before the focus group.Refreshments were offered to incentivizeparticipation.

Informed consent of all the participants wasobtained. Participants completed aprofessional demographics survey for thepurposes of describing the sample. Beforethe focus group, a brief presentationprofiled the GRASP development and

intended use with ground rules for thediscussion.25

During the focus group, we reviewed theGRASP by each body system and used adiscussion guide to facilitate conversationsabout the GRASP. Each participant wasallowed time to answer questions includingthe following: What are your initial thoughtsabout the general usefulness of this tool inthe clinical setting? Which, if any, of thedifferential diagnoses do you think can beeliminated from this tool? What, if any,differential diagnoses are we missing? Doyou think this tool would be useful in yourclinical setting? Focus groups were audio-recorded and transcribed verbatim.

Members of the study team (BLM, JCS, andSM) moderated the group sessions andrecorded field notes. After analysis of focusgroup discussions, we made edits to theGRASP.

After the revisions, the focus groupparticipants reviewed the edited GRASP toensure content and face validation.Participants were invited to complete a Web-based survey to share professional opinionsregarding the importance of eachcomponent of the revised GRASP. Consentwas embedded in the survey, and gift cardswere offered to incentivize participation.Survey questions included the following: Arethere any other additional differential

FIGURE 1 GRASP. This guide is a (not exhaustive) list of sources of pain and irritability in children with intellectual disability who are unable toverbalize symptoms or localize pain. If the patient is ill-appearing and/or is not himself or herself, a thorough evaluation as suggested inboxes A, B, and C should be done rapidly in succession. AXR, abdominal radiograph; CBC/diff, complete blood cell count with differential;CK, creatine kinase; CRP, C-reactive protein; CT, computed tomography; CXR, chest radiograph; ECG, electrocardiogram; ESR, erythrocytesedimentation rate; GI, gastrointestinal; G/J, gastro-jejunal; HCG, human chorionic gonadotropin; HIDA, hepatobiliary iminodiacetic acid;KUB, kidney ureter bladder study; MRCP, magnetic resonance cholangiopancreatography; NSAID, nonsteroidal antiinflammatory drug; PE,physical examination; PMH, past medical history; PUD, peptic ulcer disease; SSRI, selective serotonin reuptake inhibitor; UA, urinalysis;UTI, urinary tract infection; VP, ventriculoperitoneal; WOB, work of breathing; √, check.

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diagnoses you would include in the tool?Should we include any further testsin the initial workup section of thetool? On review of the survey results, thestudy team discussed participantsuggestions to improve the GRASP andrevised the tool.

Phase 2: Perception of Clinical Utility

The study team invited focus groupparticipants and medical residents of thestudy sites that provide care to childrenwith MC to test the GRASP. Participants wereasked to use the GRASP on $1 patient andthen to share their experience via a Web-based survey. Survey prompts included thefollowing: Please describe aspects of theGRASP that were most helpful; Pleasedescribe aspects of the GRASP needingimprovement; and Compared to previousevaluation practices, do you think using theGRASP helped you identify a source of pain?

Consent was embedded in the survey, andgift cards were offered to incentivizeparticipation. Again, the study teamreviewed all participant suggestions afteruse and made final adjustments to theGRASP.

RESULTSPhase 1

Twenty-six inpatient and outpatientproviders of children with MCparticipated in 4 separate focusgroup sessions at 2 pediatric hospitals.The participants were mostly medicaldoctors (n 5 14 [53.8%]) and nursepractitioners (n 5 8 [30.7%]) (Table 1). Onaverage, participants had almost 17 yearsof clinical practice, and participantsestimated caring for 23 children with MCand pain behaviors of unknown etiologyannually. Participants rated the difficultyevaluating the source of pain in children

with MC as 7.6 (SD 5 1.22, range 5 5–10)on a scale of 0 to 10.

On initial review of the GRASP, participants(N 5 26) consistently responded in supportof the GRASP and communicated the needfor this clinical tool. Participants reportedthat this tool was especially important forinexperienced clinicians, those whoinfrequently cared for children with MC, andclinicians who did not have previous clinicalexperience with the particular child withMC. Some participants reported that thistool would be helpful as a teaching tool fornew clinicians, as well as parents,guardians, and/or caregivers with concernsabout the comprehensiveness of painevaluations. During the discussions, severalparticipants recalled challenging patientsand ensured that we accounted for certaindiagnoses within the tool. Participantsprovided some suggestions for the tool,including tool organization, accessibility (eg,

FIGURE 1 (continued).

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a Web-based tool versus a paper tool), user-friendliness, and the addition of a flowdiagram.

Seven of the 12 invited participantsresponded to the Web-based survey.Respondents were mostly medical doctors(n 5 6 [85.7%]) providing inpatient care(n 5 5 [71.4%]) with over 13 years (SD 510.47, range 5 2–27) of experience andnearly 8 years (SD5 8.17, range5 1–23) ofcomplex care experience. The respondentsreported that evaluating pain in childrenwith MC was difficult (7.8 on a scale of 0 to10 [SD 5 0.75, range 5 7–9]) (Table 1).Participants again responded in support ofthe GRASP and communicated the need forthis tool in the clinical setting. They notedthat the tool would be especially helpful fornewly practicing clinicians when caring forchildren with MC in pain.

Participants offered specific suggestions formaking the GRASP more comprehensive.Participants suggested that erythrocytesedimentation rate (a marker ofinflammation) should be added to the initialworkup section of the tool. The differential

diagnosis of appendicitis was moved fromthe infection section to the gastrointestinalsection. An echocardiogram was added tothe endocarditis investigation.

Phase 2

To evaluate its clinical utility, the GRASP wasused as a trial on 14 patients who entered amedical facility for the evaluation of pain ofunknown etiology. Respondents (n5 6) weremostly medical doctors providing inpatientcare with 13 years of practice experience(SD 5 7.96, range 5 8–25) and nearly7 years (SD 5 5.15, range 5 2–15) ofcomplex care experience. On average,respondents each estimated caring for15 children (SD 5 8.01, range5 10–30) withpain behaviors of unknown origin per yearand reported a difficulty level of 7.66 (SD 50.18, range 5 7–9; Table 1) when evaluatingthese children for a source of pain.

The participants reported several benefitsof using the GRASP. All participantscommented on the utility of the checklist orframework format of the GRASP, noting thesystems-based approach was “helpful so as

not to overlook specific [differentialdiagnoses].” The organization of the GRASPby body system was especially helpful whenworking with trainees. Some respondentsfound that the GRASP helped increaseefficiencies in care, reporting that “itallowed me to be more thorough from thevery beginning in my history/physical exam,so this may have allowed me to rule outmore possibilities for source of pain morequickly.” Other respondents reported thatalthough using the GRASP lengthened theevaluation process, it was time well spentand helped them avoid unnecessaryworkups. After participant suggestions, weedited the heading of GRASP columns, addedmore specific instructions for signs andsymptoms (eg, otoscopic examinationpositive for otitis media) and consultation(eg, consult dentist for suspected dentalabscess), and incorporated emergingevaluation methods (eg, procalcitonin forcellulitis).

DISCUSSION

These results provide preliminary evidencethat the GRASP has content and face validity

TABLE 1 Participant Demographics Across Study Phases

Characteristic Focus Groups Web Survey GRASP Test

% (n) Mean (SD) Range % (n) Mean (SD) Range % (n) Mean (SD) Range

Provider type

Inpatient 30.7 (8) — — 71.4 (5) — — 66 (4) — —

Outpatient 42.3 (11) — — 28.5 (2) — — 33 (2) — —

Inpatient and outpatient 26.9 (7) — — — — — — — —

License

Medical doctor 53.8 (14) — — 85.7 (6) — — — 55 (4) —

Nurse practitioner 30.7 (8) — — 14.2 (1) — — — 33 (2) —

Physician assistant 3.8 (1) — — — — — — — —

Registered nurse 7.6 (2) — — — — — — — —

Social worker 3.8 (1) — — — — — — — —

Practice years

All practice — 16.84 (11.81) 3–37 — 13.14 (10.47) 2–27 — 13 (7.96) 8–25

Pediatric practice — 17.26 (10.6) 4–37 — — — — — —

Complex care practice — 12.56 (11.01) 0–35 — 7.85 (8.17) 1–23 — 6.83 (5.15) 2–15

Months of past year caring for children withcomplex needs

— 9.93 (3.99) 0–12 — — — — — —

Children per year cared for with pain behaviors ofunknown origina

— 23.61 (24.62) 0–100 — 15.42 (12.36) 3–40 — 15.83 (8.01) 10–30

Difficulty faced evaluating pain in children withcomplex needs

— 7.6 (1.22) 5–10 — 7.8 (0.75) 7–9 — 7.66 (0.18) 7–9

—, not applicable.a Defined as children presenting with pain behaviors with an absence of self or parent, guardian, or caregiver localization.

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in determining the source of pain inchildren with MC. This is an important firststep in tool validation for this high-riskpopulation of children who cannot verballydescribe their pain experience.

Throughout the study, participantsconfirmed the importance of such a tool forclinical care, especially related to thelimitations in obtaining self-reports in thispatient population. Typically, the patient’sself-reported history directs the medicalevaluation through first-person accounts ofsymptoms over time. On the basis of patienthistory, the use of differential diagnoses inmedicine is well established to evaluatepotential conditions that share similar signsand symptoms.26 The authors of one studyreported that 83% of diagnoses wereidentified by using only the first-personaccounts in the patient history.27 Althoughbehavioral changes in children with MCprovide valuable information to attentiveproviders and caregivers, the verbal historyof children with MC is typically third-personreports from parents andcaregivers.4,8,9,13–15,17 In most circumstances,even excellent third-person reports of thesubjective signs and symptoms are inferiorto first-person reports.28–32

During the focus group discussions,participants described the different waysthat the GRASP could be used. The obviousand original purpose is to guide theevaluation process for identifying a sourceof pain in a child with MC, depending on thechild’s presenting signs and symptoms.Clinicians can initiate this guidelinewhenever there are changes in behavior orappearance and the child appears ill andnot themselves.

The GRASP can also be used as aneducational tool for health care providersand for parents and other caregivers. Theevaluation of pain in a child with MCrequires in-depth understanding of medicalconditions and potential comorbidities.There is a need for education for providersregarding evaluating and treating pain inchildren with MC.15,33–36 Pain education, ingeneral, is limited for health care providersacross specialties and disciplines.37–41

Supervising clinicians may use the GRASP tohelp trainees gain knowledge and skills in

identifying sources of pain in children withMC.

The GRASP can also be used to educateparents. When a source of nociceptive pain isnot identified in a patient with a chronic painsyndrome, parents, guardians, or caregiversmay be worried about the lack of a positivediagnostic test result. For example, childrenwith MC may experience recurrent pain fromboth acute nociceptive sources and chronicpain without a confirmatory test to indicate asource due to the altered nervous system.Clinicians may find it helpful to share a toollike the GRASP with the parents to clearlyillustrate the evaluation and ruling-outprocesses used.

Future Research Priorities

We chose this population because childrenwith MC cannot verbally self-report andoften have potential sources of pain due toMC such as infections from implantedhardware, fractures related to osteopenia,and dysmotility from immobility. For thesereasons, children with MC were our focus inthis initial validation study. However, most ofthe differential diagnoses would certainlyapply to neurotypical children and could beuseful for preverbal children. We plan toexplore the need, if any, for a tool forpreverbal children.

As medical knowledge and diagnostic testsand interventions evolve, the GRASP willrequire periodic revision based on currentpractices and latest research. For example,some laboratory tests may be replaced bymore specific or, alternatively, moreinclusive measures. Additionally, our studywas only a first step in preparing the GRASPfor widespread adoption in the clinicalsetting. We next aim to conduct a morerigorous validation study of the GRASP.Finally, whereas parents, guardians, andother caregivers notice the changes inbehavior, activity, or affect in children withMC and seek care for their children,researchers should aim to betterunderstand the experiences of parentssurrounding pain identification andevaluation processes.

Limitations

This study was conducted with providers of2 pediatric hospitals within the same city in

the Northeast United States. One hospitalhas a specialty service for children with MC,and the other is a center specializing insubacute care for children with MC. Agreater number of inpatient providersparticipated in this initial validation thanoutpatient providers (∼66% and 33%,respectively, across study phases). In thefuture, we aim to test this tool in multiplesites with diversity in the training,experience levels, practice settings, andresources available to providers. There maybe differences in institutional proceduresand practices that may influence toollimitation. For example, serum lipase is amore specific marker for pancreatitis thanamylase. At the study institutions, amylaseand lipase are reported together, and weuse amylase as a general inflammatorymarker. Clinicians may need to modifyspecific diagnostic tests on the basis ofavailability or standards of practice ofdifferent institutions.

Additionally, in this study, we relied on theprofessional opinions and experiences ofparticipants. Respondents providing such aself-report may have answered interviewquestions and survey items on the basis ofperceived best practices and socialdesirability.

The focus of the GRASP is guiding themedical evaluation after an acute change inthe child with MC. Children with MC haverisks for comorbid acute and chronic painsources. This includes chronic sources dueto the altered nervous system, such ascentral neuropathic pain and visceralhyperalgesia. There is also the challenge ofpositive findings that may not be the sourceof pain symptoms, such as a positive cultureresult from a tracheostomy tube due tocolonization or a positive EEG result due tointractable seizures. Cognitive bias mayresult in anchoring on positive test resultsand may thereby lessen consideration ofchronic pain sources, which is an area inneed of further study.

CONCLUSIONS

Clinicians face challenges in identifyingsources of pain for children with MC. Somechallenges, such as the inability of childrenwith MC to localize or clearly state thepresence of pain, are not easily overcome.

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The GRASP can be used to systematicallyguide clinicians through a balancedapproach to a medical evaluation with agoal of determining the pain source,preventing harm, and relieving sufferingwithout unnecessary tests. Research isneeded to establish further clinical utility andto measure benefits related to length ofadmission, time to diagnosis, and otherfactors surrounding pain in children with MC.

Acknowledgments

We thank Charles Berde and Laurie Gladerfor their support of GRASP development.

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640 MORSE et al

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DOI: 10.1542/hpeds.2019-0322 originally published online July 13, 2020; 2020;10;633Hospital Pediatrics 

HauerBrenna L. Morse, Jean C. Solodiuk, Christine D. Greco, Sangeeta Mauskar and Julie

With Medical Complexity and an Unknown Source of PainInitial Validation of GRASP: A Differential Diagnoses Algorithm for Children

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DOI: 10.1542/hpeds.2019-0322 originally published online July 13, 2020; 2020;10;633Hospital Pediatrics 

HauerBrenna L. Morse, Jean C. Solodiuk, Christine D. Greco, Sangeeta Mauskar and Julie

With Medical Complexity and an Unknown Source of PainInitial Validation of GRASP: A Differential Diagnoses Algorithm for Children

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