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Early Reversal of Pediatric-Neonatal Septic Shock by CommunityPhysicians Is Associated With Improved Outcome

Yong Y. Han, MD*; Joseph A. Carcillo, MD*; Michelle A. Dragotta, RN; Debra M. Bills, RN;

R. Scott Watson, MD, MPH*; Mark E. Westerman, RT; and Richard A. Orr, MD*

ABSTRACT. Objective. Experimental and clinicalstudies of septic shock support the concept that earlyresuscitation with fluid and inotropic therapies improvessurvival in a time-dependent manner. The new AmericanCollege of Critical Care Medicine-Pediatric Advanced LifeSupport(ACCM-PALS) Guidelines for hemodynamic sup-port of newborns and children in septic shock recom-mend this therapeutic approach. The objective of thisstudy was to determine whether early septic shock rever-sal and use of resuscitation practice consistent with thenew ACCM-PALS Guidelines by community physiciansis associated with improved outcome.

Methods. A 9-year (January 1993December 2001) ret-rospective cohort study was conducted of 91 infants andchildren who presented to local community hospitalswith septic shock and required transport to ChildrensHospital of Pittsburgh. Shock reversal (defined by returnof normal systolic blood pressure and capillary refilltime), resuscitation practice concurrence with ACCM-PALS Guidelines, and hospital mortality were measured.

Results. Overall, 26 (29%) patients died. Communityphysicians successfully achieved shock reversal in 24(26%) patients at a median time of 75 minutes (when thetransport team arrived at the patients bedside), whichwas associated with 96% survival and >9-fold increasedodds of survival (9.49 [1.0783.89]). Each additional hour

of persistent shock was associated with>

2-fold in-creased odds of mortality (2.29 [1.19 4.44]). Nonsurvi-vors, compared with survivors, were treated with moreinotropic therapies (dopamine/dobutamine [42% vs 20%]and epinephrine/norepinephrine [42% vs 6%]) but notincreased fluid therapy (median volume; 32.9 mL/kg vs20.0 mL/kg). Resuscitation practice was consistent withACCM-PALS Guidelines in only 27 (30%) patients; how-ever, when practice was in agreement with guidelinerecommendations, a lower mortality was observed (8% vs38%).

Conclusions. Early recognition and aggressive resus-citation of pediatric-neonatal septic shock by communityphysicians can save lives. Educational programs that pro-

mote ACCM-PALS recommended rapid, stepwise escala-tions in fluid as well as inotropic therapies may havevalue in improving outcomes in these children. Pediat-rics 2003;112:793799; fluid resuscitation, inotropes, inter-facility transport, hydrocortisone.

ABBREVIATIONS. ACCM, American College of Critical CareMedicine; AHA, American Heart Association; PALS, PediatricAdvanced Life Support; CHP, Childrens Hospital of Pittsburgh;SBP, systolic blood pressure; PRISM, Pediatric Risk of Mortality;PICU, pediatric intensive care unit.

Experimental and clinical studies of septic shocksupport the concept that persistent shock hasan adverse impact on survival in a time-depen-

dent manner.14 Recently, a randomized, controlledstudy of adult septic shock showed that early aggres-sive goal-directed resuscitation in the emergency de-partment improves outcome.5 Although comparablerandomized studies in children are lacking, the re-ported pediatric literature has been consistent with

both experimental studies and the adult experience.We previously reported a role for early, aggressivefluid resuscitation in pediatric septic shock.6 Nadel et

al7

(at St. Marys Hospital in London, England) at-tributed poor outcome from severe meningococcaldisease to delayed recognition and treatment. Booyet al8 extended their findings at St. Marys Hospital

by reporting decreased mortality from meningococ-cal disease over a 6-year period from 23% to 2% afterthey had implemented a community hospital-basededucation and resuscitation program with special-ized, pediatric critical care transport.

In this regard, the American College of CriticalCare Medicine (ACCM) recently published its Clini-cal Practice Parameters for Hemodynamic Support of Pe-diatric and Neonatal Patients in Septic Shock,9 which has

been incorporated into the American Heart Associa-tions (AHA) Pediatric Advanced Life Support (PALS)Provider Manual.10 The ACCM-PALS Guidelines callfor rapid, stepwise execution of therapeutic interven-tions with the goal to restore normal blood pressureand perfusion within 1 hour of patient presentation9

(Fig 1). Whether these new ACCM-PALS Guidelineswill be effective in reversing shock and improvingoutcome in pediatric-neonatal septic shock remainsto be determined. To begin to examine this question,we reviewed the interfacility transport database atChildrens Hospital of Pittsburgh (CHP) to deter-mine whether early resuscitation and reversal of pe-diatric-neonatal septic shock by community hospital

From the Departments of *Critical Care Medicine and Pediatrics, Univer-

sity of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; and De-

partment of Critical Care Medicine/Transport, Childrens Hospital of Pitts-

burgh, Pittsburgh, Pennsylvania.

Preliminary work for this study was presented, in part, at the Society of

Critical Care Medicine 29th Educational and Scientific Symposium; Febru-

ary 1115, 2000; Orlando, FL; and at the Pediatric Academic Societies and

American Academy of Pediatrics Joint Meeting; May 1216, 2000; Boston,

MA.

Received for publication Nov 18, 2002; accepted Apr 2, 2003.

Reprint requests to (J.A.C.) Department of Critical Care Medicine, Chil-

drens Hospital of Pittsburgh, 3705 Fifth Ave, Pittsburgh, PA 15213. E-mail:

[email protected]

PEDIATRICS (ISSN 0031 4005). Copyright 2003 by the American Acad-

emy of Pediatrics.

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physicians is associated with improved outcome. Wealso examined the potential relevance of the new

ACCM-PALS Guidelines to current resuscitation prac-tice by community hospital physicians.

METHODS

Patient Selection, Study Definitions, and DataCollected

The Human Rights Committee of CHP granted exemption ofinstitutional review for this study. A 9-year (January 1, 1993December 31, 2001), retrospective review of the CHP transportteams interfacility transport database was performed. We identi-fied infants and children with sepsis through a query of thedatabase using the terms sepsis, septic shock, meningococ-cemia, and bacteremia. Transport records were then reviewedto determine which patients met clinical criteria for septic shock,9

which was defined by suspected infection as manifested by hy-perthermia or hypothermia and signs of decreased perfusion,including decreased mental status, prolonged capillary refill time,diminished peripheral pulses, or mottled extremities. Althoughnot necessary to meet criteria, the presence of hypotension and useof inotropic/vasopressor infusions to maintain normotensionwere considered confirmatory signs of decreased perfusion. Allpatients were transported to CHP by CHPs pediatric critical caretransport team. Premature infants 36 weeks corrected gesta-tional age were excluded from the study.

Hypotension was defined as systolic blood pressure (SBP) less

than the fifth percentile for age, using the formula taught inPALS.9 Prolonged capillary refill time was defined as 3 seconds.Shock reversal was defined by normalization of both SBP andcapillary refill time. Appropriate fluid therapy was defined as theadministration of any volume of fluid that resulted in successfulshock reversal or 60 mL/kg when the patient remained in per-sistent shock. Resuscitation was considered to have been consis-tent with the new ACCM-PALS Guidelines when therapeutic inter-ventions performed by community physicians had been similar tothe stepwise algorithm covering the first hour of resuscitation (seeFig 1).

Demographic, epidemiologic, and outcome data were recordedfor each patient. Clinical assessments were extracted from trans-port records at 3 time points: 1) transport team arrival at thepatients bedside, 2) transport team departure from the commu-nity hospital, and 3) transport team return to our institution. Theseassessments were used to determine whether shock reversal had

been achieved and whether resuscitation had been consistent withthe new ACCM-PALS Guidelines for each transport time point.Using the time of initial call requesting transport as reference,duration of persistent shock (beyond the time of call) and delayin resuscitation consistent with ACCM-PALS Guidelines were de-termined and categorically scored into 1-hour increments. Thefrequencies that community hospital physicians executed specifictherapeutic interventions were also recorded.

The Pediatric Risk for Mortality (PRISM) score11 is widelyconsidered the gold standard tool to assess severity of illnessin pediatric intensive care units (PICU) in the United States andmany parts of the world. PRISM is scored from 14 routinely

Fig 1. The ACCM Clinical Practice Parameters for Hemodynamic Support of Pediatric and Neonatal Patients in Septic Shock stepwise manage-

ment of recommended therapeutic interventions during the first 60 minutes of resuscitation. (Adapted from Carcillo and Fields9).

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measured physiologic variables in a PICU setting and is calculatedusing the worst physiologic values observed during the first 24hours after admission. PRISM scores were determined and re-corded for our study patients as per scoring guidelines. Accord-ingly, patients who did not survive to 24 hours after admission tothe PICU were not assigned a PRISM score. Mortality was definedas both transport and hospital mortality.

Statistical Analysis

The computer statistical software program Jandel SigmaStat(version 2.0) was used for data analysis. Differences betweengroups were assessed by Mann-Whitney rank sum tests for con-tinuous variables and by 2 or Fisher exact tests for categoricaldata. Multiple logistic regression analyses, adjusting for severityof illness (PRISM scores), were performed to determine whether 1)shock reversal was associated with increased survival, 2) resusci-tation consistent with the new ACCM-PALS Guidelines was asso-ciated with increased survival, 3) duration of persistent shock wasassociated with increased mortality, and 4) delay in resuscitationconsistent with ACCM-PALS Guidelines was associated with in-creased hospital mortality. Severity-of-illness (PRISM) adjustedsurvival and mortality odds ratios with 95% confidence intervalswere calculated using standard mathematical formulas.

RESULTS

During the 9-year study period, CHPs pediatriccritical care transport team performed 6196 trans-ports; 186 (3%) transports involved infants and chil-dren with sepsis. Among these transports, 91 pa-tients met criteria for septic shock, which accountedfor 49% of the transported sepsis population and1.5% of the total transport population. Fifty-three(58%) patients with septic shock presented with hy-potension, 54 (59%) patients presented with pro-longed capillary refill time, and 36 (40%) patientspresented with both at the time of call. The charac-teristics of these patients with septic shock are pre-sented in Table 1. A comorbid condition was presentin 36 (40%) patients. The most common conditionamong these patients related to neurologic/muscu-loskeletal disease in 11 (31%) patients, followed by

hematologic/oncologic disease in 8 (22%) patients,chromosomal/congenital disease in 7 (19%) patients,immunologic disease in 5 (14%) patients, and otherdisease in 5 (14%) patients. Identification of specificinfectious cause was possible in 65 (71%) patients.Among these patients, the primary organism wasisolated from blood in 42 (65%) patients, cerebrospi-nal fluid in 5 (8%) patients, trachea/lung in 8 (12%)patients, urine in 5 (8%) patients, peritoneum in 2(3%) patients, and other sites in 3 (5%) patients.

A total of 26 patients died, accounting for an over-

all mortality rate of 29%. Among these 26 nonsurvi-vors, 2 (8%) patients died at the referring communityhospital, 1 died before transport team arrival, 1 wasreceiving active cardiopulmonary resuscitation asthe team arrived and subsequently died before teamdeparture, and 1 died in the first 24 hours of thePICU stay. The PRISM scores (median [25th75thpercentile]) were significantly greater among non-survivors (26 [1336]) versus survivors (11 [4 17];P .001). There were no differences in microbialcause for nonsurvivors (Staphylococcus aureus [n 3],S epidermidis [n 1], group B streptococcus [n 4],S pneumoniae [n 1], group A streptococcus [n 1],Gram-positive cocci [n 2], meningococcus [n 1],Klebsiella [n 1], Bacteroides fragilis [n 1], Gram-negative bacilli [n 2], Aspergillus [n 2], Mucor-mycosis [n 1], Enterovirus [n 1], herpes simplexvirus [n 1]) compared with survivors (S epidermidis[n 4], viridans streptococcus [n 2], group Bstreptococcus [n 6], Listeria [n 1], group A strep-tococcus [n 1], Gram-positive cocci [n 1], Hae-mophilus influenza type B [n 1], meningococcus [n7], Escherichia coli [n 3], Klebsiella [n 1], B fragilis[n 1], Citrobacter [n 2], Pseudomonas [n 5], P

mirabilis [n 1], Candida albicans [n 1], C parapsi-losis [n 1], Enterovirus [n 2], herpes simplexvirus [n 1], respiratory syncytial virus [n 2], H

pylori [n 1]). No significant differences were ob-served regarding other characteristics among non-survivors and survivors (Table 1).

Resuscitative efforts by community hospital phy-sicians resulted in successful shock reversal in 24(26%) patients by the time that the transport teamarrived at the patients bedside (median time: 75minutes). Successful shock reversal by communityphysicians was associated with 96% survival (Fig 2A)and 9-fold increased odds of survival (PRISM

score-adjusted; Table 2). Community hospital physi-cians had implemented therapies consistent with thenew ACCM-PALS Guidelines during the resuscitationof 27 (30%) patients. Resuscitation consistent withthe new ACCM-PALS Guidelines was associated with93% survival (Fig 2B) and 6-fold increased odds ofsurvival (PRISM score-adjusted; Table 2). Each hourof persistent shock that passed was associated with2-fold increased odds of mortality (PRISM score-adjusted), and each hour of delay in institution ofresuscitation consistent with ACCM-PALS Guidelines

TABLE 1.Characteristics of Children With Septic Shock

Patients(n 91)*

Survivors(n 65)*

Nonsurvivors(n 26)*

P Value

Age (mo) 22 [1131] 24 [1130] 12 [0156] .651Male sex (n [%]) 45 (49) 31 (48) 14 (54) .765Comorbid condition (n [%]) 36 (40) 26 (40) 10 (38) .919PRISM score 13 [624] 11 [417] 26 [1336] .001Culture-positive sepsis (n [%]) 65 (71) 47 (72) 18 (69) .971Physician on transport (n [%]) 79 (87) 56 (86) 23 (88) 1.000Time to transport team arrival at

community hospital (min)75 [49114] 74 [47113] 80 [51121] .613

Total transport time (min) 191 [133253] 186 [133253] 200 [131262] .694

* Continuous data are expressed as median [25th75th percentile]. From time of initial call requesting transport. p .001 survivor versus nonsurvivor.

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was associated with a 50% increased odds of mortal-ity (PRISM score-adjusted; Table 2).

Table 3 presents the frequencies that community

hospital physicians executed specific therapeutic in-terventions for patients who presented in septicshock. Overall, community physicians had adminis-tered appropriate fluid therapy to fewer than half(45%) of these patients and had performed resusci-tation consistent with the new ACCM-PALS Guide-lines in fewer than one third (30%). Fluid and inotro-pic therapies administered by community physiciansdid not significantly differ between patients whoseshock was successfully reversed when comparedwith those whose shock persisted. Consequently,community physicians had administered appropri-ate fluid therapy (25%) and had performed resusci-

tation consistent with the new ACCM-PALS Guide-lines (4%) to even fewer patients with persistentshock. Community physicians infused hydrocorti-sone therapy to a minority of children (13%) duringtheir resuscitation. However, hydrocortisone therapytrended toward successful shock reversal amongthese patients (50% with hydrocortisone vs 23%without hydrocortisone; P .074 Fisher exact test).

Community physicians had implemented for non-survivors (when compared with survivors) signifi-cantly more mechanical ventilatory support (73% vs38%), dopamine/dobutamine infusions (42% vs20%), and epinephrine/norepinephrine infusions(42% vs 6%). However, community physicians had

administered similar fluid therapy (both in volumeadministered and appropriateness) to both nonsur-vivors and survivors and ultimately had performedresuscitation consistent with the new ACCM-PALSGuidelines-directed therapy to significantly fewernonsurvivors when compared with survivors (8% vs38%). Survival rate was similar among patients whodid (67%) and did not (72%) receive hydrocortisonetherapy in the community hospital emergency de-partment setting.

DISCUSSION

Early Shock Reversal Is Associated With ImprovedOutcome

The results of our study support the hypothesesthat early shock reversal and resuscitation consistentwith the new ACCM-PALS Guidelines by communityphysicians can be associated with improved out-come. We report that when community physicianshad implemented therapies that resulted in success-ful shock reversal (within a median time of 75 min-utes), almost all of the infants and children whopresented with septic shock survived. We also ob-

served that the odds of mortality doubled with eachhour of persistent shock that passed and that eachhour of delay in resuscitation consistent with ACCM-PALS Guidelines was associated with a 50% increasedodds of mortality for our study population regard-less of underlying severity of illness measured by thePRISM score.

Our findings are consistent with the study by Riv-ers et al,5 who showed that when early goal-directedtherapies were implemented in the emergency de-partment, survival outcomes in adult septic shocksignificantly improved. Although the specific thera-peutic targets of central venous pressure between 8

and 12 mm Hg, mean arterial pressure between 65and 90 mm Hg, urine output 0.5 mL/kg/h, andcentral venous oxygen saturation 70% in the study

by Rivers et al5 differed from our study (which tar-geted normal SBP for age and normal capillary refilltime), the overall therapeutic goal of achieving rapid,hemodynamic optimization was conceptually simi-lar. The present study builds on our groups previ-ous work, which reported that rapid, aggressivefluid resuscitation of pediatric septic shock withinthe first hour of presentation to the emergency de-partment was associated with improved outcome.6

Our results also agree with the study by investiga-

tors at St. Marys Hospital in London, England, whofound that avoidable delays and inappropriate treat-ments contributed to poor outcome among childrenwith severe meningococcal disease.7 Shock had not

been recognized or treated in 50% of these patients.7

Collectively, these findings have important impli-cations for the pediatric population because manychildren live in communities without a pediatric-specialized center nearby, and subsequently theymust access care through their local community hos-pital.12 It is likely that the initial resuscitation thatcommunity hospital physicians provide will have thegreatest impact on determining the survival outcomefor children who present with septic shock. For this

Fig 2. A, Shock reversal from resuscitative efforts by communityhospital physicians resulted in 96% survival versus 63% survivalamong patients who remained in persistent shock state. B, Resus-citation consistent with the new ACCM-PALS Guidelines resultedin 92% survival versus 62% survival among patients who did notreceive resuscitation consistent with the new ACCM-PALS Guide-lines. *P .001 versus shock reversed; P .001 versus resusci-tation consistent with ACCM-PALS Guidelines.


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reason, immediate, aggressive resuscitation of chil-dren with septic shock should be the communityphysicians first priority rather than delaying resus-citation while awaiting transfer to a pediatric-referralcenter.

Fluid Resuscitation Practice May Not Be Adequate inthe Community Hospital Setting

Our study suggests that fluid resuscitation practicein community hospitals remains conservative. Weobserved that community physicians administeredsimilar median volumes of fluid therapy (20.0mL/kg vs 23.9 mL/kg) to both patients in persistentshock and patients whose shock was reversed. Thissuggests that community physicians tend to admin-ister a 20-mL/kg bolus of fluid during the initialresuscitation of pediatric-neonatal septic shock butthen do not administer additional fluid boluses topatients who remain in persistent shock. When facedwith particularly severe cases of septic shock (ie,nonsurvivors), community physicians seem to esca-

late preferentially to inotropic/vasopressor supportrather than administer additional fluid therapy. Al-though most children in septic shock certainly re-quire inotropic/vasopressor support, the hemody-namic impact of catecholamine infusions may be

blunted by inadequate fluid resuscitation.6 The rea-son for this limited fluid resuscitation by commu-nity physicians remains to be determined. However,its practice partly explains the paradoxical findingthat despite having received increased inotropic/vasopressor support, nonsurvivors in this studywere less likely to have received resuscitation con-sistent with the new ACCM-PALS Guidelines. Theseguidelines speculate that stepwise escalation of ther-

apies, starting with airway management and ade-quate fluid resuscitation, will improve survival out-comes in pediatric-neonatal septic shock.

Does Hydrocortisone Therapy Have a Role in TreatingSeptic Shock in the Community Hospital Setting?

We note that community physicians in our studyadministered hydrocortisone therapy to 13% of the

patients in septic shock. Although it did not reachstatistical significance, the use of hydrocortisonetended to be associated with greater shock reversal,lending support for a possible role for this therapy inthe treatment of septic shock. This concept has beena topic of considerable interest and active investiga-tion. It is widely recognized that certain patients areat risk for adrenal insufficiency secondary to an in-adequate hypothalamic-pituitary-adrenal axis re-sponse from prolonged corticosteroid use or from anexisting central nervous system abnormality. Adre-nal insufficiency can also occur in the presence ofpurpura fulminans particularly during fatal menin-

gococcal septic shock.13,14

One randomized con-trolled trial that examined the role of high-dose hy-drocortisone (50 mg/kg intravenous bolus followed

by a 50-mg/kg infusion over 24 hours) in Dengueshock syndrome found significant survival bene-fit.15,16 Hydrocortisone provides both glucocorticoidand mineralocorticoid effect. A randomized con-trolled trial of the pure glucocorticoid dexametha-sone found no effect on the outcome in African chil-dren with sepsis.17 The ACCM-PALS Guidelinesrecommend empiric treatment with hydrocortisoneinfusion in children with catecholamine-resistantshock and purpura fulminans or other risk factors foradrenal insufficiency.

TABLE 2. Multiple Logistic Regression Analyses: Survival and Mortality Odds Ratios With 95%Confidence Intervals (Adjusted for PRISM Score)

Variable SurvivalOdds Ratio

MortalityOdds Ratio

95% ConfidenceInterval

Shock reversed 9.49 1.0783.89Resuscitation consistent with ACCM-PALS Guidelines 6.81 1.2636.80Duration of persistent shock (per 1-h increment) 2.29 1.194.44Delay resuscitation consistent with ACCM-PALS

Guidelines (per 1-h increment) 1.53 1.082.16

TABLE 3. Frequencies of Specific Therapeutic Interventions Implemented by Community Hospital Physicians

Therapeutic Intervention All Patients(n 91)

ShockReversed(n 24)

PersistentShock

(n 67)

Survivors(n 65)

Nonsurvivors(n 26)

Mechanical ventilation (n [%]) 44 (48) 9 (38) 35 (52) 25 (38) 19 (73) P .01Intraosseous line (n [%]) 8 (9) 1 (4) 7 (10) 5 (8) 3 (12)Central venous line (n [%]) 27 (30) 8 (33) 19 (28) 17 (26) 10 (38)Fluid therapy (mL/kg)# 20.0 [9.249.2] 23.9 [12.244.7] 20.0 [8.257.5] 20.0 [9.340.0] 32.9 [6.464.1]Appropriate fluid therapy (n [%]) 41 (45) 24 (100) 17 (25)* P .001 32 (49) 9 (35)Dopamine or dobutamine (n [%]) 24 (26) 5 (21) 19 (28) 13 (20) 11 (42) P .05Epinephrine or norepinephrine (n [%]) 15 (16) 2 (8) 13 (19) 4 (6) 11 (42) P .001Glucose (n [%]) 9 (10) 1 (4) 8 (12) 6 (9) 3 (12)Bicarbonate (n [%]) 23 (25) 5 (21) 18 (27) 13 (18) 10 (38) P .059Hydrocortisone (n [%]) 12 (13) 6 (25) 6 (9) P .074 8 (12) 4 (15)Resuscitation consistent with ACCM-PALS

Guidelines (n [%])27 (30) 24 (100) 3 (4)* P .001 25 (38) 2 (8) P .01

* P .001, P .074 versus shock reversed. P .001, P .01, P .05, P .059 versus survivors.# Data are expressed as median (25th75th percentile).

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Can ACCM-PALS Guidelines Be Relevant toCommunity Practice?

Although prospective studies will need to be con-ducted to determine definitively whether the new

ACCM-PALS Guidelines will be effective in improv-ing outcome in pediatric-neonatal septic shock, ourstudy lends support for its application to the com-munity hospital setting. However, because these new

ACCM-PALS Guidelines were developed in pediatricacademic centers without specific regard for the

community physician, barriers to its successful trans-lation and implementation into the community hos-pital setting may exist. One barrier could be relatedto specialized technical skills needed to execute spe-cific therapies. For example, not all health care pro-viders who care for children possess sufficient pedi-atric airway management skills to perform oralendotracheal intubation. Also, some communityphysicians may not be comfortable placing centralvenous lines in critically ill children. However, theserequisite technical skills did not seem to restrict theexecution of these therapeutic interventions by com-munity physicians in our study. Community physi-cians placed 73% of the nonsurvivors on mechanicalventilatory support and obtained central venous ac-cess in 38%. Rather, it seems that important, educa-tional barriers might play a greater role in curtailingthe implementation of the new ACCM-PALS Guide-lines in the community setting. We observed thatmany community physicians provided limited fluidtherapy to patients in persistent shock. Educationalprograms and future revisions of the ACCM-PALSGuidelines as well as the PALS curriculum will needto address these and other potential barriers to im-plementation in the community hospital setting.

It is likely that through ongoing, cooperative ef-forts between community hospitals and specialized,

tertiary-care pediatric referral centers, these newACCM-PALS Guidelines can be implemented success-fully. Support for this view comes from Booy et al,8

who described an impressive reduction of mortalityfrom meningococcal disease in southern Englandfrom 23% to 2% in a span of just 6 years. This im-proved case fatality rate occurred without anychange in severity of illness defined by PRISMscores. This remarkable improvement in outcomecan be attributed to improved health care deliverythrough a combination of dissemination of recom-mended guidelines for managing meningococcal dis-ease (see Pollard et al18) to area community hospitals

through educational outreach programs, facilitationof early communication and management recom-mendations between the local and referral hospital,and utilization of a mobile pediatric critical caretransport team.8

Practical Measures That Community Physicians CanUse to Recognize and Treat Children With SepticShock

It has been estimated in a recent epidemiologicstudy of severe sepsis in the United States that42 000 annual cases, almost 4400 annual deaths,and annual costs on the order of $1.97 billion can be

attributed to severe sepsis in children.19 The commu-nity physician can perform many important, life-saving interventions that are well within the scope oftheir community-based practice to help these chil-dren. Septic shock can be recognized in its earlieststages as tachycardia, bounding peripheral pulses,and altered mental alertness. In later stages, pro-longed capillary refill time occurs, and still later,hypotension develops as these earlier compensatorymechanisms begin to fail. The community physicianshould strive to recognize and treat shock beforehypotension occurs. If the child has no hepatomegalyor rales, then aggressive fluid resuscitation should beadministered with rapid successions of 20-mL/kg

boluses of isotonic crystalloid (eg, normal saline) orcolloid (eg, 5% albumin) up to 60 mL/kg or untilresolution of shock. Rapid blood glucose evaluationshould be simultaneously performed and hypogly-cemia corrected with glucose administration. Inotro-pic therapies can be administered through the pe-ripheral vein, intraosseous route, or central venousaccess. Dobutamine (5 g/kg/min) can be adminis-tered through the peripheral vein to improve capil-lary refill in normotensive patients8,18; however, in

hypotensive patients, dopamine and, commonly,epinephrine infusion is required. Because infants andchildren have an age-specific insensitivity to dopa-mine, our transport team uses epinephrine only. Thegreatest efficacy is attained when epinephrine is in-fused through a central line (begin at 0.10 g/kg/min); however, in children without central access,the intraosseous route can be used. Hydrocortisoneshould be given to children who are at risk for ad-renal insufficiency, including children with purpurafulminans.

In the meantime, the regional pediatric center canbe contacted for additional recommendations and

arrangements can be made for possible transfer to aPICU, preferably using a pediatric-specialized trans-port team. In areas where telemedicine technology isavailable, pivotal decisions regarding the initial man-agement of the child in shock can be facilitatedthrough interactive conversations between the com-munity physician and telemedicine commandphysician.

Study Limitations

Our study has several limitations to consider. First,its retrospective nature brings inherent restrictionswith regard to the strength of our conclusions. How-

ever, for at least 1 of our observations (persistentshock is associated with increased mortality), a ret-rospective study may be the only practical method toexamine this relationship. Second, we have relied onclinical rather than laboratory or invasive hemody-namic parameters to define shock reversal. We chosethis approach because we favored the idea of usingsimple, bedside assessments that could be adoptedand practiced easily by community physicians.Third, to determine the duration of persistent shock,we made the assumption that patients presented tothe community hospital at the onset of their symp-toms. In fact, we are uncertain when each child be-came ill and how long he or she may have been in


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shock before being brought to medical attention. It isalso uncertain when in relation to patient presenta-tion the request for interfacility transport by the com-munity hospital physician was actually made.Fourth, because the definitions of appropriate fluidtherapy and delay in resuscitation consistent with

ACCM-PALS Guidelines were coupled to the condi-tion of shock reversal, an inherent bias was intro-duced regarding the application of these definitionsto outcome. However, not all patients need the fullgamut of therapeutic interventions during resuscita-tion of septic shock. For some patients, fluid therapymay be the only therapy needed; for others, inotropicsupport with dopamine may be necessary; and inothers, epinephrine may be required. In this regard,we contend that these definitionsalthough by nomeans idealserve their function in permitting amethod to assess appropriateness of escalations intherapy. Fifth, it is possible that our study popula-tion was not truly representative of pediatric-neona-tal septic shock in the community hospital. By virtueof needing transport to our tertiary-care pediatricreferral center, only the most severe cases of septicshock may have been selected from each community

hospital. Sixth, because previous clinical experienceof the community physicians was not assessed, it isunknown whether physicians with more experiencetended to resuscitate earlier with more success. Sev-enth, we do not have data on initial antibiotic choiceand do not know the degree to which this influencedoutcome.

CONCLUSIONS

Pediatric septic shock is a life-threatening illnessthat requires immediate recognition and aggressivetreatment in the community hospital setting. Therecently published ACCM Clinical Practice Parameters

for Hemodynamic Support of Pediatric and Neonatal Pa-tients in Septic Shock provides a stepwise algorithmthat community physicians can incorporate into theirpractice of pediatric-neonatal septic shock resuscita-tion. Successful implementation of these guidelineswill likely require educational efforts to increasephysician comfort with early administration of ag-gressive fluid resuscitation. Future studies will beneeded to address potential barriers to guideline im-plementation and to determine its efficacy in thecommunity hospital setting.

ACKNOWLEDGMENTS

Funding for this work was provided by Emergency MedicalServices for Children, Maternal and Child Health Bureau Grant1-MCH-4240030-01-0 (R.A.O.); a Laerdal Foundation for AcuteMedicine grant (R.A.O.); and National Institutes of Health grants3M01RR0056GCRC (J.A.C.) and T32-HD40686 (Y.Y.H.).

We thank Robert W. Hickey, MD, Patrick M. Kochanek, MD,Ann E. Thompson, MD, and Shekhar T. Venkataraman, MD, forconstructive, critical reviews of the preliminary manuscript. Wethank the members of Childrens Hospital of Pittsburghs Trans-port Team for dedication to the safe transport of critically illinfants and children and for meticulous maintenance of the trans-port database.

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