RAPID VERSUS SLOW REWARMING FOR MANAGEMENT OF MODERATE TO SEVERE - - PowerPoint PPT Presentation
RAPID VERSUS SLOW REWARMING FOR MANAGEMENT OF MODERATE TO SEVERE HYPOTHERMIA IN LOW BIRTH WEIGHT PRETERM NEONATES - A RANDOMIZED CONTROLLED TRIAL Dr Prerana Jain, MD Pediatrics, Department of Pediatrics Pt B D Sharma Post Graduate Institute of
Dr Prerana Jain, MD Pediatrics, Department of Pediatrics Pt B D Sharma Post Graduate Institute of Medical Sciences, Rohtak Dr Jagjit Dalal, Associate Professor, Department of Pediatrics And Neonatology Pt B D Sharma Post Graduate Institute of Medical Sciences, Rohtak
■ Temperature loss in a newborn will result in neonatal hypothermia with serious and potentially fatal consequences if not prevented or managed appropriately.1 ■ Rewarming is a key step to prevent life threatening morbidities and mortality in hypothermic neonates. ■ But evidence is lacking regarding optimal method for attaining normothermia, whether rapid rewarming or slow rewarming should be done. ■ The traditional recommendation has been that slow rewarming is preferable to rapid rewarming to avoid complications such as apnea and arrhythmias.2-5 ■ Other studies2,6-9 have shown that a combination of neonatal intensive care plus rapid rewarming under a radiant warmer resulted in minimal mortality.
■ There is no direct study available for which mode to prefer between slow and rapid rewarming in moderate to severe hypothermia cases, specially in low resource countries like India where servo control radiant warmers are also not widely available. ■ So we planned a study to evaluate the effect of rapid versus slow rewarming in management of moderate to severe hypothermia in LBW preterm neonates in our hospital’s emergency setting.
■ Aim The aim of the study was to evaluate the effect of rapid versus slow rewarming in management of moderate to severe hypothermia in LBW preterm neonates. ■ Objectives of study:
1. Primary objective: Compare the effect of rapid versus slow rewarming in moderate - severely hypothermic low birth weight preterm neonates as assessed by stabilization score at baseline, 6 hours and 24 hours of enrollment. [TOPS (temperature, oxygenation, perfusion, saturation) and MSNS (modified sick neonatal score) scores] and mortality at 24 hours of enrolment and during hospital stay till discharge or death. 2. Secondary objective: Compare the proportion of neonates developing morbidities like sepsis, NEC (necrotizing enterocolitis), IVH (intraventricular hemorrhage), RDS (respiratory distress), hypoglycemia, apnea, need for intubation or respiratory support; time to reach normal body temperature (normothermia) and rewarming rate between the two groups.
■ The study was done in the Department of Pediatrics, PGIMS Rohtak from September 2017 to December 2018. Ethical clearance was obtained from the Institutional Board of Studies. A pre informed consent was obtained from either of the parents. ■ Type of study: Randomized controlled trial, open label. ■ A total of 100 low birth weight preterm neonates weighing <2.5kg and gestation <37week with axillary/ skin temperature of <36oC presenting within the first 72 hours of life were included in the study and randomized into two groups by computer generated random sequence numbers; group A received rapid rewarming (@ >0.5oC/hr ) and group B received slow rewarming (@ ≤0.5oC/hr) after attaining 34oC, till normothermia (36.5oC) is achieved by the neonates.
Moderate to severe hypothermia (<36oC)
Assessed for eligibility Randomised Exclusion criteria
weight
death before normothermia
acceptable representative (LAR) not giving consent to participate
with refractory shock
Group B
Undergo slow rewarming (≤0.5oC/hr) a) If temperature <34oC: rewarming under radiant warmer till 34oC; after that slow rewarming at @0.5oC/hr till 36.5oC skin temperature (5hr) b) If temperature is between 34- 35.9oC: keep directly under servo control mode for slow rewarming at 0.5oC/hr
Group A
Undergo rapid rewarming (>0.5oC/hr) under radiant warmer in servo control mode till the skin temperature reaches 36.5oC.
Secondary
Primary outcome Secondary
Primary outcome
Compared and evaluated
Figure 1 Diagram showing the flow of patients
Continous HR, RR, SpO2, temperature monitored
■ Sample Size: A sample size of 50 in each group over a period of 1 year was taken. The sample size was calculated using Epilnfo software. ■ Statistical Analysis: Data obtained was analysed by statistically standard tests. Statistical testing was conducted with the statistical package for the social science system version SPSS 17.0.
■ TOPS includes: a. Temperature by digital thermometer in axilla or skin
c. Perfusion by capillary refilling time (CFT) on mid-sternum d. Sugar by reagent strip and low reading glucometer <40mg/dl.10 ■ Hypothermia, hypoxia, prolonged CFT and hypoglycaemia were defined as <36.5°C11, <90%12, ≥ 3 seconds13 and < 40 mg/dl, respectively. ■ All the four parameters were assessed at baseline, 6 hours and 24 hours post admission of each subject and TOPS score was calculated along with the change in TOPS score since admission.
■ MSNS score is essentially a modification of another validated scoring system, Sick Neonate Score and studied among transported neonates. ■ It has 8 parameters, each given a score of 0 to
implied the best possible clinical setting for each of the parameters.14
Parameter Score 0 Score 1 Score 2 Respiratory effort Apnoea or grunt Tachypnoea (respiratory rate >60/min) with or without retractions Normal (respiratory rate 40–60/min) Heart rate Bradycardia or asystole Tachycardia (>160/min) Normal (100– 160/min) Axillary temperature (°C) <36 36–36.5 36.5–37.5 Capillary refilling time (s) >5 3-5 <3 Random blood sugar (mg/dl) <40 40-60 >60 Maximum Spo2 (%) <85 85-92 >92 Gestational age (in weeks) <32 weeks 32 to 36 weeks + 6/7 days 37 weeks and above Birth weight (kg) <1.5 1.5-2.49 2.5 or above Total Maximum 16
Table I Parameters of MSNS with scoring for each parameter 14
In our study, total 267 neonates presented in casualty over a period of 1 year. Out of them, 100 neonates were included in the study (Figure 2).
Figure 2 Algorithm showing inclusion of patients
74 neonates excluded with no/mild hypothermia 193 neonates with moderate-severe hypothermia Accessed for eligibility 100 neonates included 100/119 neonates included Low birth weight neonates <2.5 kg Gestation <37 week Presenting within 72 hours of life 100 neonates Randomised 50 neonates Group A Rapid rewarming 50 neonates Group B Slow rewarming 267 neonates presented in casualty
74 neonates excluded
<1 Kg weight (22)
(17)
normothermia (0)
acceptable representative (LAR) not giving consent to participate (3)
with refractory shock (32)
■ All the foetal and maternal baseline characteristics were equally distributed amongst the two groups and statistically not significant. ■ Statistically significant difference was found in the rewarming rates and rewarming time between the two groups. The mean rewarming rate in group A was 0.11 ± 0.07 (oC/min), while in group B it was 0.012 ± 0.002 (oC/min) (p value <0.001), with calculated odds ratio being 0.097 (0.07- 0.12). ■ Mean rewarming time taken in rapid rewarming group was 28.72 ± 28.90 min and in slow rewarming group was 157.78 ± 107 min. p value calculated was <0.001 (statistically significant). ■ Primary outcome was assessed by stabilization score (TOPS and MSNS score) and mortality at 24 hours of enrolment and during hospital stay till discharge or death. ■ TOPS score was used at baseline, 6 hours and 24 hours post admission to assess the stabilization
Mean MSNS score in rapid rewarming group was 9.92 ± 1.91 and in slow rewarming group was 10.14 ± 1.93, with a p value of 0.569 (95% CI = 9.37 - 10.46). The results were also statistically not significant at 6 hours and 24 hours post admission, between the two groups. (p value= 0.476 and 0.333, respectively) as described in Table II.
MSNS Score Rapid rewarming (mean ± SD) Slow rewarming (mean ± SD) p- value MSNS score at admission 9.92 ± 1.91 10.14 ± 1.93 0.569 MSNS score at 6 hours 12.18 ± 1.88 12.06 ± 1.85 0.476 MSNS score at 24 hours 12.08 ± 1.72 12.12 ± 1.69 0.333
Table II Stabilization assessed as per MSNS score at admission, 6 hours and 24 hours after admission
Total mortality in group A was 7 (14%) and in group B was 5 (10%). (p value=0.538). There is also no significant difference in mortality between the two groups when calculated within 24 hours and more than 24 hours of hospital stay. (Table III)
Mortality Rapid rewarming (n=50) n (%) Slow rewarming (n=50) n (%) OR (95% CI) p value Total mortality 7 (14.0) 5 (10.0) 1.46 (0.43-4.97) 0.538 Mortality within 24 hours 4 (8.0)1 1 (2.0) 4 (0.21-75.65) 0.343 Mortality >24 hours 3 (6.0) 4 (8.0) 0.78 (0.16-3.73) 0.762
Table III Mortality in rapid and slow rewarming group
Secondary
Rapid rewarming (n=50) n (%) Slow rewarming (n=50) n (%) OR (95% CI) p value Hypoglycaemia 7 (14.0) 3 (6.0) 2.55 (0.62-10.49) 0.182 Hypocalcaemia 3 (6.0) 3 (6.0) 1 (0.19-5.21) 1 Shock 11 (22.0) 11 (22.0) 1 (0.38-2.57) 1 Respiratory distress 32 (64.0) 36 (72.0) 0.69 (0.29-1.60) 0.392 Seizures 8 (16.0) 8 (16.0) 1 (0.34-2.91) 1 Apnoea 9 (18.0) 8 (16.0) 1.15 (0.40-3.27) 0.790 Metabolic acidosis at admission 15 (30.0) 19 (38.0) 0.40
acidosis at 24 hours 11 (23.91) 12 (24.49) 0.95
24 h 6 (12.0) 3 (6.0) 0.468 (0.11- 1.98) 0.295 Hospital stay >24h 44 (88.0) 47 (94.0) Need for ventilation 8 (16.0) 2 (4.0)
found in all the short term secondary
(Table IV).
haemorrhage (IVH) and necrotising enterocolitis (NEC) were not seen in any of the patients in both the groups.
Table IV Secondary neonatal outcomes
Primary neonatal
Moderate Hypothermia (Temp =32-35.9oC) p- value Severe Hypothermia (Temp<32oC) p- value Rapid rewarming (mean ± SD) Slow rewarming (mean ± SD) Rapid rewarming (mean ± SD) Slow rewarming (mean ± SD) TOPS at admission 1.29 ± 0.46 1.13 ± 0.34 0.08 1.77 ± 0.97 1.5 ± 0.79 0.48 TOPS at 6 h 0.12 ± 0.45 0.13 ± 0.34 0.91 0.66 ± 1 0.33 ± 0.49 0.32 Change in TOPS (0-6 h)
0.12
0.87 TOPS at 24 h 0.29 ± 0.46 0.27 ± 0.56 0.87 0.00 0.5 ± 0.53 0.04 Change in TOPS (0-24 h)
0.37
0.36 MSNS score at admission 10.29 ± 1.70 10.68 ± 1.52 0.28 8.22 ± 1.98 8.41 ± 2.15 0.83 MSNS score at 6 hours 12.53 ± 1.48 12.58 ± 1.60 0.90 10.55 ± 2.65 10.41 ± 1.67 0.88 MSNS score at 24 hours 12.02 ± 1.80 12.56 ± 1.52 0.16 12.5 ± 1.04 10.75 ± 1.48 0.02 Mortality 4 (9.76) 1 (2.63) 0.194 3 (33.33) 5 (41.67) 1
■ Rewarming rate and time in both the subgroups (moderate and severe hypothermia) was statistically highly significant (p value <0.001) between rapid and slow rewarming groups. ■ Statistically significant difference was not found in subgroup analysis of any of the other primary and secondary outcome variables (except, rewarming rate and rewarming time). (Table V, VI)
Table V Subgroup analysis on primary neonatal outcomes
Secondary neonatal outcome
Moderate Hypothermia (Temp =32-35.9oC) Severe Hypothermia (Temp<32oC) Rapid rewarming (n=41)/ % Slow rewarming (n=38)/% OR (95% CI) p-value Rapid rewarming (n=9)/% Slow rewarming (n=12)/% OR (95% CI) p-value
Hypoglycaemia
5 (12.2) 3 (7.89) 1.62 (0.36-7.30) 0.527 2 (22.2) NA
3 (7.32) 2 (5.26) 1.42 (0.22- 9.00) 0.709 1 (8.33) NA
8 (19.51) 6 (15.79) 1.29 (0.40- 4.14) 0.665 3 (33.33) 5 (41.67) 0.7 (0.11- 4.23) 0.697
Respiratory distress
23 (56.10) 25 (65.79) 0.66 (0.26-1.65) 0.378 9 (100.00) 11 (91.67) 1 0.375
Seizures
7 (17.07) 8 (21.05) 0.77 (0.25-2.38) 0.652 1 (11.11) 0 (0.00) NA
6 (14.63) 3 (7.89) 2 (0.46- 8.63) 0.346 3 (33.33) 5 (41.67) 0.7 (0.11- 4.23) 0.697
Hospital stay (24 h)
2 (4.88) 3 (7.89) 1.67 (0.26-10.59) 0.582 4 (44.44) 0 (00.00) NA
(oC/min)
0.11 ±0.08 0.01 ± 0.002 <0.001 0.89 ± 0.05 0.01 ± 0.001 <0.001
Rewarming time (min)
18.41 ± 14.80 102.26 ± 41.96 <0.001 75.66 ± 31.56 333.58 ± 26.76 0.0001
Table VI Subgroup analysis on secondary neonatal outcomes
■ In the present study, the mean duration of rewarming using radiant warmer in skin mode was 28.72 ± 28.90 min in rapid rewarming group. While in slow rewarming group, it was 157.78 ± 107 min, with a p value of <0.001. In a study done by Feldman et al (2016), median rewarming time was 1 hour with an interquartile range of 0.6–2.4 hours.15 Kaplan et al conducted a similar study in 1984 on 18 infants with birth weight >750 gm and found the mean time required to rewarm the infants to rectal temperature of 36.5oC was 3.96 ± 2.37 hours.6 ■ In the current study, the rewarming rate calculated in group 1 was 0.11 ± 0.07 (oC/min), while in group 2 it was 0.012 ± 0.002 (oC/min). (p value <0.001) statistically highly significant, with calculated odds ratio being 0.097 (0.07-0.12). Feldman et al calculated median rewarming rate of 1.5oC/hour, in the study conducted on 98 infants in 2016. In the study by Kaplan et al, the mean rate of rewarming was 1.8o± 1.37o per hour.6
■ TOPS and MSNS scores, used to assess primary outcome in neonates in both the groups had comparable results. At present, there is no study in which these scores were used to assess the
■ The earlier comparative studies had important limitations. They were dated, conducted in different settings, and they enrolled patients with different baseline characteristics (postnatal age, GA, outborn/ inborn, and degree of hypothermia). ■ Furthermore, the quality of these studies was poor in terms of number of enrolled patients, study design, and outcome measures. No definitive conclusion for treatment of cold-compromised infants can be drawn. ■ The rewarming rate could have been affected by the attending nurse’s management as well as by the individual response of the subject. This aspect could not be explored because of the retrospective nature of most of the studies.2
■ The limitations of present study include, small sample size and the setting of the study. Patients admitted in NICU were not included in the study. ■ The strength of our study is the characteristics of population, (VLBWIs) with both moderate and severe hypothermia were included in the study.
Rapid rewarming with less time is as good as slow rewarming for hypothermic neonates in terms of stabilization score, mortality and short term neonatal outcomes. So it can be a preferred mode of rewarming in low resource setting countries like India, where servo control radiant warmers are not widely available and burden of hypothermic neonates is very high.
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6. Kaplan M, Eidelman AI. Improved prognosis in severely hypothermic newborns treated by rapid
7. Mathur NB, Krishnamurthy S, Mishra TK. Estimation of rewarming time in transported extramural hypothermic neonates. Indian J Pediatr 2006; 73:395-9. 8. Daga SR, Gajendragadkar A, Chutke P, Kamat H. Rapid rewarming of severely hypothermic newborns during initial stabilization. Acta Paediatr 1994; 83:263-4. 9. Sargant N, Sen ES, Marden B. Too cold for comfort: a neonate with severe hypothermia. Emerg Med J 2012; 29:420-1
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Birth Weight Infants with Admission Hypothermia. PLoSone 2015; 10:e0131976.
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Baseline characteristics Rapid rewarming (n=50) Slow rewarming (n=50) Age at admission (mean ± SD) (hours) 25.08 ± 21.17 22.48 ± 16.06 Mean birth weight (mean ± SD) (grams) 1836.80 ± 480.13 1857.20 ± 456.25 Mean gestation (mean ± SD) (weeks) 33.82 ± 2.53 34.0 ± 2.30 Gender n (%) Male Female 27 (54.0) 23 (46.0) 32 (64.0) 18 (36.0) Parity n (%) 1 2 ≥3 30 (60.0) 10 (20.0) 10 (20.0) 30 (60.0) 6 (12.0) 14 (28.0) Multiple birth n (%) 1 (single) 2 (twins) 43 (86.0) 7 (14.0) 48 (96.0) 2 (4.0) Mode of delivery n (%) Cesarian Vaginal 9 (18.0) 41 (82.0) 8 (16.0) 42 (84.0) Resuscitation n (%) Initial steps Positive pressure ventilation 43 (86.0) 7 (14.0) 42 (84.0) 8 (16.0) Premature rupture of membranes 10 (20.0) 5 (10.0) Antepartum hemorrhage 1 (2.0) 3 (6.0) Maternal Fever 1 (2.0) Clinical Chorioamnionitis 2 (4.0) 3 (6.0) Oxytocin Induction Labor Onset (Spontaneous) 48 (96.0) 50 (100.0) Prolonged Labor 1 (2.0) Cord Around Neck 2 (4.0) 2 (4.0) Meconium stained liquor 6 (12.0) 8 (16.0) Cord Prolapse Instrumentation 1 (2.0) Dai Handling 1 (2.0) Prematurity 26 (52.0) 22(44.0) Very low birth weight 15 (30.0) 12 (24.0) Asphyxia 6 (12.0) 12 (24.0) Malformations Sepsis 15 (30.0) 11 (22.0) Neonatal jaundice 9 (18.0) 11 (22.0) Unbooked/Supervised 9 (18.0) 12 (24.0)
Table Baseline characteristics
TOPS score Rapid rewarming (mean ± SD) Slow rewarming (mean ± SD) p-value TOPS score (admission) 1.38 ± 0.60 1.22 ± 0.50 0.153 TOPS score (6 hours) 0.22 ± 0 .61 0.18 ± 0.38 0.698 Change in score (6 hours)
0.285 TOPS score (24 hours) 0.25 ± 0.44 0.32 ± 0.56 0.566 Change in score (24 hours)
0.280
Table Stabilisation assessed as per TOPS score
Dopamine requirement At admission At 6 h P value At 24 h P value Rapid rewarming No Yes (n=50) n (%) (n=50) n (%) 0.60 (n=46) n (%) 0.85 42 (84.0) 8 (16.0) 40 (80.0) 10 (20.0) 38 (82.6) 8 (17.4) Slow rewarming No Yes (n=50) n (%) (n=50) n (%) 0.55 (n=49) n (%) 0.04 49 (98.0) 1 (2.0) 48 (96.0) 2 (4.0) 43 (87.75) 6 (12.24) P value 0.014 0.014 0.479
Table Patients requiring dopamine at admission, 6 hours and 24 hours after admission in the two groups