What Are the Indications for Administering Intravenous Fluids to Resuscitate Children

What are the indications for administering intravenous fluids to resuscitate children and young people with suspected meningococcal septicaemia?

What are the clinical indications for giving inotropes in children and young people with suspected/confirmed bacterial meningococcal septicaemia?

Bibliographic information / Study type & evidence / Study details / Number of patients / Characteristics of studies/patients / Intervention & comparison / Follow up & outcome / Results & effect size / Reviewer comment /
Ninis et al., 2005 116 / Case–control study
Evidence level: 2++ / Aim: To determine whether suboptimal management/healthcare delivery in the first 24 hours after admission to hospital
could contribute to poor outcome in children
with meningococcal disease.
Setting: Hospitals in England, Wales and Northern Ireland.
Inclusion criteria: Data from national statistics and hospital records used to identify cases of meningococcal disease in children aged 0–16 years between 1 December 1997 and 28 February 1999 in England, Wales and Northern Ireland. Children were defined as probable, possible or confirmed case of meningococcal disease using definitions from the public health Laboratory Meningococcus Working group.
Confirmed by discussion with consultants in
disease control and the consultant responsible for the patient. Hospital medical and nursing records reviewed to confirm diagnosis. / 143 cases (children under 17 years who died from
meningococcal disease) and 355 controls (survivors).
. / For each death (case), three controls (survivors) from the same region were matched for age (1, 1–4, 5–14, and 15–16 years) corresponding to different risks of mortality. / Compared hospital care in fatal and non-fatal cases using hospital medical and nursing records.
Care was recorded retrospectively using a standardized form: clinical presentation, vital signs, laboratory results and treatments initiated were recorded for each hour after admission for 24 hours.
A panel of paediatricians blinded to the outcome assessed case records using a standardised form and scored patients for suboptimal management using predefined criteria for optimal management. Criteria were based on published and nationally accepted protocols of care.
Failure of care: defined as delay of more than an hr between the action recommended by the panel and action taken at hospital. Either because of failure to recognise the complication or failure to recognise severity of complication.
Failure in supervision: defined as delay of more than 24 hrs in being seen by a consultant.
The panel scored all patients on admission with the Glasgow meningococcal septicaemia prognostic score (GMSPS) and
assigned patients to three groups: meningitis, septicaemia or a mixed picture.
–Predefined complications included –cardiovascular failure: hypotension if blood pressure below normal range for age, if no
hypotension then signs of two organ failures; CNS failure, respiratory failure, metabolic
acidosis >5, capillary refill time >3 seconds, or toe-core temperature gap >3°.
Optimal management for cardiovascular failure defined as:
–fluid therapy: 40 ml/kg in first hour given in aliquots of 20 ml/kg.
–If signs of shock persist, intubate and start mechanical ventilation.
–start peripheral inotropes (dopamine or dobutamine).
–If poor response to volume resuscitation and peripheral inotropes start adrenalin infusion through central line.
–fluids: 20 ml/kg also recommended if features of compensated shock (increased capillary refill and tachycardia, but patient not meeting full definition for cardiovascular failure). / Comparison of groups at baseline:
Similar ages and similar frequency of serogroup B.
141/143 [98%] of non-survivors noted to have organ failure versus 169/355 [48%] of non-survivors. P value not reported.
Univariate analysis:
Probability of death was significantly correlated with: –GMSPS as a dichotomous and categorical variable, P < 0.001
–septicaemia versus meningitis, P = 0.001.
Failures in management (departure from optimal management protocols) were significantly more common in children who died than in survivors.
The following failures in management were significantly associated with death:
–Failure to recognise disease complications:
OR 2.1 [95% CI 1.3 to 3.2], P = 0.001
–Failure to appreciate disease severity:
OR 2.2 [95% CI 1.4 to 3.4], P = 0.001
–Failure in supervision by consultant:
OR 2.1 [95% CI 1.2 to 3.5], P = 0.007
-Lack of involvement of paediatric team in care:
OR 4.6 [95% CI 2.1 to 11], P < 0.001
–Inadequacies of fluid administration (bivariate analysis controlled for need for fluid):
too little versus adequate fluid therapy:
OR 2.5 [95% CI 1.4 to 4.7], P = 0.004
–Inadequate inotropes (bivariate analysis controlled for needing inotropes):
OR 5.8 [95% CI 2.3 to 14], P < 0.001.
Multiple treatment failures significantly increased the risk of death.
Multivariate analysis:
Adjusted for the following potential confounders:
GMSPS, organ failure, disease type (septicaemia or meningitis), meningococcal serogroup, and the need for fluid or inotrope therapy as potential confounders found three independent risk factors for death:
–Not being under the care of a paediatrician:
OR 66.0 [95% CI 3.6 to 1210], P = 0.005
–Failure of supervision by consultant:
OR 19.5 [95% CI 1.8 to 213], P = 0.015
–Failure to administer adequate inotropes:
OR 23.7 [95% CI 2.6 to 213], P = 0.005.
–Not being under the care of a paediatrician was highly correlated with a failure to recognise complications, P = 0.002.
–When absence of paediatric care was removed from the model, failure to recognise disease complications became significant: OR 6.1 [95% CI 1.7 to 22],
P = 0.006.
40ml/kg of fluid in the first hour given in aliquots of 20 ml/kg, followed by mechanical ventilation and administration of peripheral inotropes (dopamine or dobutamine) if shock persisted. In the event of a poor response to volume resuscitation and peripheral inotropes the protocol recommended starting an adrenaline infusion. / Funding: Partly supported by a grant from the Meningitis Research Foundation.
Multivariate analysis performed to account for
potential confounders such as disease severity (Glasgow meningococcal
septicaemia prognostic score), disease type, serogroup,
organ failure, and whether the patient needed fluid or inotrope
therapy.
Wide confidence intervals.
Authors’ conclusion:
suboptimal health care delivery significantly reduces the likelihood of survival in children with meningococcal disease.
Han et al.,
2003 117 / Retrospective cohort study
Evidence level: 2– / Retrospective cohort study conducted over 9 years (from January 1993 to December 2001).
Aim: to determine whether:
–early resuscitation and reversal of septic shock by community hospital physicians is associated with increased survival
–resuscitation practice consistent with the
American College of Critical Care Medicine (ACCM)–Pediatric Advanced Life Support Guidelines published in 2002 is associated with improved outcome in children
–duration of persistent shock is
associated with increased mortality,
–delay in resuscitation
consistent with ACCM–PALS Guidelines is associated with increased mortality.
Setting: Community hospitals in the US.
Data extracted from the Children’s
Hospital of Pittsburgh (CHP) transport
team database.
Inclusion criteria:
Clinical criteria for septic shock:
suspected infection manifested by hyperthermia
or hypothermia and signs of decreased perfusion,
including decreased mental status, prolonged capillary refill time > 3 sec,
reduced peripheral pulses, or mottled extremities.
All patients were transported to CHP by CHP’s paediatric critical care
transport team.
–Hypotension and use of inotropes/ or vasopressors to maintain normotension
were considered confirmatory signs of decreased perfusion.
Excluded: Premature infants < 36 weeks’ corrected gestational
age. / 91 infants and children with septic shock.
. / 91 infants and children with septic shock who required transport to Children’s
Hospital of Pittsburgh from community hospitals.
Age: mean age = 22 months (25th to 75th percentile: 1–131 months)
A co-morbid condition was present
in 36/91 [40%] patients:
–11 children [31%] had neurological/
musculoskeletal disease
–8 children [22%] had haematological/oncological disease
–7 children [19%] had chromosomal/congenital disease
–5 children [14%] had immunological disease.
–Organism identified in
65 [71%]
children.
Organism was
isolated from: –blood in 42 [65%] children
–cerebrospinal
fluid in 5 [8%] –trachea/lung in 8 [12%]
–urine in
5 [8%]
–peritoneum in 2 [3%]
–other sites in 3 [5%] of children.
Aetiology included Gram negative and positive bacterial infection, viral and fungal infection. / –Shock reversal: defined by return
of normal systolic blood pressure and capillary refill
time to < 3 sec.
–Resuscitation practice consistent with ACCM–PALS
Guidelines.
–Appropriate fluid therapy: defined as the
administration of any volume of fluid that resulted in successful
shock reversal or ≥ 60 ml/kg when the patient remained in persistent
shock.
–Resuscitation considered to be consistent
with the 2002 ACCM–PALS Guidelines when therapeutic interventions
performed by community physicians were similar to
the stepwise algorithm covering the first hour of resuscitation.
The ACCM–PALS Guidelines recommends the
rapid, stepwise execution of interventions
to restore normal blood pressure
and perfusion within 1 hour of presentation. This includes aggressive and early fluid management with crystalloid or colloid boluses up to and over 60ml/kg.
Also includes within the first hour:
–commencing dopamine if fluid refractory shock present
–in the case of fluid refractory, dopamine-resistant shock:
commencing epinephrine for cold shock and commencing norepinephrine for warm shock. / –Hospital and transport mortality.
Information about clinical assessments were extracted from database at 3 time points:
1) transport team arrival at the patient’s bedside
2) transport team departure from the community
hospital
3) transport team return to CHP.
Assessments were used to determine whether shock reversal had been achieved and whether resuscitation had been consistent with the ACCM–PALS Guideline for each time point.
–PRISM score recorded if child survived 24 hrs. / Mortality:
26/91 [29%] children died.
2 children [8%] died at the referring community
hospital, 1 died before transport team arrival, 1 was
receiving active cardiopulmonary resuscitation as
the team arrived and subsequently died before team
departure, and 1 died in the first 24 hours of the
PICU stay.
Comparison of survivors and non-survivors:
The PRISM score (median [25th–75th
percentile]) was significantly higher in the non survivor group compared with survivors (26 [13–36]) for survivors versus (11 [4–17] for survivors],
P < 0.001).
–No significant difference in age, sex, proportion of children with co-morbid condition, time to transport team arrival, or total transport time between survivors and non-survivors (all P values non significant).
–No significant differences in aetiological organism for survivors versus non-survivors: meningococcus was isolated from 1 non-survivor and from 7 survivors.
Survival: comparison of cohorts:
There was successful shock reversal by community hospital physicians in 24/91 [26%] patients by the time that the transport team arrived at the patient’s bedside (median time: 75 mins).
–Successful shock reversal in the first hour of resuscitation was significantly associated with improved outcome: 96% survival for shock reversal versus 63% survival for persistent shock state:
OR 9.49 [95% CI 1.07 to 83.89], P < 0.001.
OR adjusted for PRISM score.
–Resuscitation consistent with the 2002 ACCM–PALS Guideline in 27/91 [30%] of patients.
–Resuscitation consistent with the 2002 ACCM–PALS Guideline was significantly associated with improved outcome: 92% survival for those given care consistent with the guideline versus 62% survival for patients who did not receive resuscitation consistent with the guideline:
OR 6.81 [95% CI 1.26 to 36.80], P < 0.001.
OR adjusted for PRISM score.
–Each additional hour of persistent shock was associated with > 2-times increased odds of mortality: adjusted OR 2.29 [95% CI 1.19 to 4.44].
–Each hour of delay in institution of resuscitation consistent with ACCM–PALS Guidelines was associated with a 50% increased odds of mortality: adjusted OR 1.53 [95% CI 1.08 to 2.16]. / Funding: Grants from Emergency Medical Services for Children, Maternal and Child Health Bureau; Laerdal Foundation for Acute Medicine; National Institutes of Health.
Retrospective study: high risk of bias and of confounding.
Multiple logistic regression analyses adjusting for severity
of illness using PRISM scores were performed.
PRISM score assesses severity during first 24 hours of admission, not prior to resuscitation therefore confounding of severity not adequately adjusted for.
No comparison of severity of illness at baseline prior to commencement of resuscitation.
Retrospective cohort study with limited comparison between cohorts. Most of the analyses compare survivors versus non survivors without adjustment for confounders.
Appropriate fluid therapy is defined by successful reversal of shock, therefore comparisons of the adequacy of fluid resuscitation in children with shock reversal versus persistent shock is not useful.
Doesn’t include information about missing data or other sources to substantiate diagnosis and outcome.
Duration of shock: as acknowledged by authors, duration measurements make the assumption that shock starts on presentation to hospital. No record of duration of shock prior to admission.
Inwald et al., 2009 111 / Retrospective case series (clinical audit)
EL=3 / Aim: to assess management in pre-PICU services of severe sepsis in children in the UK compared to ACCCM-PALS guideline.
Setting: 17 PICUs and 2 PICU retrieval units over 6 months
Inclusion criteria: children with provisional diagnosis of sepsis (systemic inflammatory response syndrome in the presence of, or as a result of, suspected or proven infection) accepted for PICU admission within 12h of arrival in hospital.
Exclusion criteria: children in whom sepsis was not a discharge diagnosis. / 200 children met inclusion criteria / 58% male
median age 13.6 months (IQR 2.9 – 39.4 months)
54% had +ve bacteriological culture or PCR test for bacteriological pathogen.
16% had viral culture / Shock reversal
Death in PICU / Median inter-hospital transport time: 7.6h (IQR 5.3 – 11.7).
By time of inter-hospital transfer or PICU admission:
–92% mechanically ventilated
–69% had received inotropic support
–12% had received RRT
–4% had received ECMO
70% had signs of shock at time of referral to PICU
–53/139 (38%) reversed shock by time of PICU admission
–83/139 (60%) failed to reverse shock or died by time of PICU admission
–missing data on 3 children
Comparison between shock reversal (n=53) and no shock reversal (n=83)
Median age (months) 9.8 vs 15.1 p=0.02
Median WCC (106/l) 9.0 vs 10.3 p=0.77
Median platelets (106/l) 264 vs 183 p=0.001
Median C-reactive protein (mg/l) 63 vs 76 p=0.41
Median blood glucose (mmol/l) 5.6 vs 5.6 p=0.41
Median PaO2/FiO2 ratio (Hg mm) 255 vs 310 p=0.5
Survivors (%)= 50 (94%) vs. 62 (75%)
p=0.03
Presence of shock after inter-hospital transfer was the only independent predictor of death after admission to the paediatric intensive care unit (PICU; OR for death 3.8, 95% CI 1.4 to 10.2, p=0.008).