Over Hydration In Diabetic Ketoacidosis Essay

Over-hydration in diabetic ketoacidosis (DKA)

may increase the risk of cerebral edema in

children.

Design Prospective descriptive study

Patients Thirty-nine pediatric patients (1 month–16 years) presenting with 42 episodes of DKA.

Intervention Clinical and biochemical variables were collected on admission. Dehydration was calculated by measuring acute changes in body weight during the period of illness.

Results The median (25th–75th centiles) magnitude of dehydration at presentation was 5.7% (3.8–8.3%) (mean±SD 6.8±5%). Neither the initial clinical assessment nor the comprehensive biochemical profile at admission correlated with the magnitude of dehydration. Despite considerable variation in the degree of dehydration and biochemical disequilibrium, all patients recovered from DKA within 24 hrs with a standardized therapeutic approach. Over Hydration In Diabetic Ketoacidosis Essay. Furthermore, therapidity of patient recovery did not correlate with the magnitude of dehydration on presentation or the amount of fluid administered (median (25th–75th centiles) 48.8 ml/kg (38.5–60.3)) in the first 12 h

Conclusion The magnitude of dehydration in DKA is not reflected by either clinical or biochemical parameters. These findings need confirmation in larger studies

INTRODUCTION.

Diabetic ketoacidosis (DKA) is a life-threatening condition that develops when cells in the body are unable to get the sugar (glucose) they need for energy, such as when you have diabetes and do not take enough insulin. Without insulin, the body cannot use sugar for energy. When the cells do not receive sugar, the body begins to break down fat and muscle for energy. When this happens,ketones, or fatty acids, are produced and enter the bloodstream, causing the chemical imbalance (metabolic acidosis) called diabetic ketoacidosis. Under- administration and over-administration of fluid may increase patient morbidity by delaying the correction of DKA3 or by increasing the risk of cerebral edema, respectively. 2 Consequently, the magnitude of dehydration in DKA is of major interest and continues to be a subject of research.4

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While measurement of the acute change in body weight is accepted as the gold standard for determining the magnitude of dehydration,4 6 this is seldom feasible. Therefore, the total loss of body water has typically been inferred from clinical

and biochemical variables that mainly reflect the intravascular fluid volume state.4 5 7–9 In DKA, this approach may be inadequate as the hyper osmolar state acts to preserve the intravascular volume. Furthermore, perturbation of the hemodynamic state, which can attend severe metabolic acidemia, may also confound the clinical estimation of fluid loss.Over Hydration In Diabetic Ketoacidosis Essay.  Indeed, previous studies,4 5 although limited to a small number of biochemical and clinical variables, failed to show reliable biochemical and clinical predictors of the magnitude of dehydration. Recent guidelines do not promote individual fluid status determination but rather recommend the assumption of 7–10% dehydration in all patients presenting in DKA unless the patient is haemodynamically unstable.1 5 10 11 In this study, we undertook an assessment of the magnitude of dehydration (estimated by change in body weight) in children in DKA at the

time of presentation, and sought to determine associations between comprehensive clinical and laboratory variables and the degree of dehydration.

MATERIALS AND METHODS

We conducted a prospective study of consecutive patients aged 1 month–16 years, diagnosed with DKA, who presented to the emergency department in a Xinxiang medical university hospital

from January 2010 to February 2012.The study was approved by the Ethics Committee of the First Affiliated Hospital of Xinjiang Medical University, this study was done in the declaration of Helsinki.

. Patients were excluded from the study when patient and/or parental consent was not obtained, or when fluid replacement therapy had begun prior to weighing the patient. DKA was defined as a pH <7.3 (venous), a glucose >11 mmol/l, calculated

bicarbonate (HCO3) of <15 mmol/l and the presence of urine ketones.1 Recovery from DKA was defi ned as HCO3 ≥18 mmol/l. Blood gases were assessed at least every 2 h in the first

12 h and at least every 4 h in the next 24 h. The following clinical variables were collected on admission: demographics, heart rate, arterial blood pressure, capillary refill time and level of consciousness using the Glasgow Coma Scale (GCS). The laboratory results recorded on admission included: blood gases, glucose, hemoglobin, haematocrit, electrolytes, osmolality, creatinine, blood urea nitrogen (BUN), HbA1c, albumin and lactate levels. The osmolar gap (measured osmolality−calculated osmolality) was calculated. 12 Sodium (Na+) was corrected for glucose level ([Na+]+([ glucose]−5.6)/5.6)×1.6). Deviation of the heart rate and blood pressure from the mean and maximum normal values for age were calculated for each patient.12 Weight was obtained on admission before fluid administration (admission weight). Over Hydration In Diabetic Ketoacidosis Essay.

and every 12 h thereafter until discharge from hospital (discharge weight) and until two consecutive similar weights (0.5%) were obtained (final weight). In the absence of two

consecutive similar weights, the patient’s weight within 7 days after discharge was considered as the final weight. The magnitude of dehydration was defined as the % loss of

body weight (LBW) ((discharge weight−admission weight)/ discharge weight×100).. An average of three readings were recorded. The calculated coefficient of variation (SD/

mean×100) of the scales was a mean of 0.21% for patients over 15 kg and 0.34% for those under 12 kg. After the study, we retrospectively examined the charts for the actual amount of fluid administered to each patient. For determining the percentage of fluid above maintenance, the

maintenance amount of fluid was calculated according to the following: 100 ml/kg for the first 10 kg, 50 ml/kg for the next 10–20 kg and 20 ml/kg thereafter12 All patients were managed according to a pre-existing provincial management protocol (endorsed by the Province of china xinjiang) for fluid, insulin and electrolyte administration In brief, on admission, each patient initially received 10 ml/kg measured weight of 0.9% saline, repeated as necessary until hemodynamic stability was achieved as judged by the responsible physician. This was followed by an infusion o f 0.9% or 0.45% saline at a rate of 4–6 ml/kg/h (independent of age and urine output) until DKA resolved. Potassium and

glucose were added to the solution as necessary.

Table 1 Demographic characteristics of all analyzed patients on admission with diabetic ketoacidosis episodes

Age (years)

11 (5–16)

New diabetes (%)

52.6

Male (%)

47.8

Weight (kg)

35.4 (18.3–56.9)

Fluid (ml/kg/12 h)*

52.9 (45.0–66.7)

Fluid over calculated maintenance (%)

107 (51–148)

Calculated degree of dehydration (%)

5.7 (3.7–8.1)

Length of stay (h)

30 (24–48)

Duration of symptoms (days)

5.0 (2–16)

PCCU admission (%)

21.1

pH

7.12 (7.05–7.22)

Na+ (mmol/l)

133 (130–135)

Na+ corrected (mmol/l)

140.4 (136.9–143.9)

Glucose (mmol/l)

33.3 (25.2–43.6)

Chloride (mmol/l)

96.5 (94–103)

Haematocrit 0.44 (0.41–0.48)

0.44 (0.40–0.48)

Hemoglobin (mg/dl)

13.3 (12.3–14.7)

*First 12 h including resuscitation fluid. PCCU, pediatric

Statistical analysis

SPSS V.16.0 was used for data analysis. Categorical data were summarized as percentages. The results were reported as medians (25th–75th centiles). Over Hydration In Diabetic Ketoacidosis Essay.

The Pearson correlation coefficient was used to assess the relationship between normally distributed continuous variables, and Spearman’s who was used for skewed continuous

variables. The χ2 test or Fisher’s exact test was used to compare differences in proportions for categorical variables. The independent samples t test was used to compare mean differences

in normally distributed continuous outcomes, and the Mann–Whitney U test was used to compare skewed continuous variables between categorical independent variables. A p value of <0.05 was considered statistically significant except when the Bonferroni adjustment was made for multiple comparisons.

RESULTS

During the study period, 49 patients with 53 episodes of DKA were managed in our centre. Six patients had commenced treatment prior to arrival and were not eligible for the study. Four

of the 43 eligible patients declined to participate. Therefore, 39 patients with 42 episodes of DKA were successfully enrolled and completed the study.

Demographics

Demographic data are provided in table 1. All patients had type 1 diabetes. Nine of the patients (21%) were admitted to the pediatric intensive care unit. The rest were admitted to

the pediatric medicine department. Only three patients (7.35 %) presented with a GCS <13. One patient (2.69%) presented with mild hypothermia (32.9°C) and required mechanical ventilation. Over Hydration In Diabetic Ketoacidosis Essay.

No patient experienced a decreased GCS after initiation of therapy and all had attained a GCS >13 within 12 h of commencing treatment

TABLE 2

Association between demographic, clinical and biochemical variables recorded on admission and magnitude of dehydration

Categorical variables p* Value

PCCU admission

0.783

New diabetes

0.623

Lactate >2.2 mmol/l

0.748

Continuous variables

r Value

p‡ Value

Age (years)

−0.192

0.216

pH 0.146 0.363

0.1444

0.360

HCO3 0.057 0.720

0.055

0.718

Glucose

0.203

0.200

Sodium [Na+]

0.355

0.018

Corrected sodium [Na+]

0.501

0.001

Potassium (K+)

0.210

0.172

Creatinine

0.207

0.179

Blood urea nitrogen

0.276

0.071

CO2

0.040

0.790

Creatinine

0.209

0.179

Creatinine†

0.281

0.065

Anion gap

0.047

0.632

Anion gap (corrected)

0.050

0.752

HbA1c

−0.028

0.870

Osmolality

0.223

0.151

Osmolality (gradient)

0.003

0.984

Fluid (ml/kg/12 h)

0.111

0.477

Fluid (% above maintenance)

0.011

0.935

Mean heart rate†

0.041

0.777

Respiratory rate

− 0.118

0.448

Mean blood pressure†

− 0.101

0.427

Length of stay

0.097

0.557

Duration of symptoms

−0.154

0.307

*Calculated using the t test and Mann–Whitney U test.

†Levels above normal values corrected for age.

‡Calculated using the Pearson correlation coefficient for normally distributed

continuous variables; Spearman’s rho was used for skewed continuous variables. Over Hydration In Diabetic Ketoacidosis Essay.

PCCU, pediatric critical care unit

Correlation of dehydration with biochemical or clinical

parameters on admission

In the study population, the median (25th–75th centiles) magnitude of dehydration, based on LBW, was 5.7% (3.7–8.3%) (range 1.4–24.8%) or 8.9% (6.0–13.5%) (range 1.9–41.0%) when corrected for % of total body water. In 20/42 (48%) episodes, parents had noted weight loss in their child. No

significant correlations were found between the patient’s demographic variables (age, duration of symptoms, new versus known diabetes), clinical variables (deviation of heart rate

from maximal rate corrected for age or deviation of mean arterial blood pressure corrected for age) or biochemical variables (pH, HCO3, glucose, CO2, HbA1c, creatinine and BUN deviation

from maximum normal values, anion gap, corrected anion gap, osmolar gap and the presence of lactic acidosis) recorded on admission and the magnitude of dehydration, whether

based on LBW or corrected for % of total body water (table 2). Sodium and corrected sodium level were the only biochemical variables to show reasonable correlation with severity of

dehydration (r=0.35, p=0.02 and r=0.502, p=0.001, respectively). Although no significant correlation between patient age and the magnitude of dehydration was observed across the whole group, when we subdivided the patients, based on age, into those ≤2 years and >2 years of age, the magnitude of dehydration in children ≤2 years of age (n=6) was significantly greater whether expressed in LBW (9.7% (6.2–11.8%) vs 5.3% (3.5–7.4%), p=0.014) or corrected for total body water (15.2% (10.5–18.5%) vs 8.3% (5.5–10.7%), p=0.016). Over Hydration In Diabetic Ketoacidosis Essay.

Categorizing the magnitude of dehydration to non-severe

and severe

Severe dehydration (LBW ≥6% in children, ≥10% in infants)12 was detected in 18/42 (43%) patients. The main characteristics of patients with non-severe (mild, moderate) and severe

dehydration are presented in table 3. Except for the corrected [Na+] on admission, no significant differences were observed between groups.

Correlation between magnitude of dehydration and amount

of fluid administered

In the first 12 h, fluids were administered exclusively via the intravenous route. The median (25th-75th centiles) volume of administered during the first 12 h was 52.9 ml/kg (45-66.4 ml/kg). No correlation was detected between the total amount of fluid administered or the amount of fluid administered

above maintenance and the magnitude of dehydration (figure 1). There was, however, a negative correlation between the amount of fluid administered during therapy and the pH on admission (r=−0.44, p<0.05). Over Hydration In Diabetic Ketoacidosis Essay.

Resolution of DKA

In all patients, DKA resolved within 24 h (figure 2). No significant elations were found between the patient’s age, versus known diabetes, glucose level, osmolar gap, presence

of lactic acidosis, magnitude of dehydration on admission r amount of fluid administered in the first 12 h (whether expressed as ml/kg or % above maintenance) and the rapidity

of recovery from DKA (figure 2). However, there was a significant negative correlation between the level of HCO3 on admission and time to recovery (r=−0.74, p<0.001).

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DISCUSSION

Fluid replacement is the cornerstone of therapy in DKA. Work n animal models demonstrates that successful fluid replenishment lone will reverse many of the clinical and biochemical

derangements seen in DKA.Over Hydration In Diabetic Ketoacidosis Essay.  However, precise fluid therapy is often impeded by difficulties in the determination f the magnitude of dehydration in DKA and differences in

opinion regarding the need to account for on-going fluid (urinary) loss. The mean magnitude of dehydration observed in his study is similar to that reported in previous studies4 and

supports current recommendations to assume a 7–10% depletion n total body water when managing patients in DKA.1 14 hese recommendations are based mainly on two studies

performed in 195215 and 193316 in a small number of patients. he observation that children ≤2 years of age had a significantly higher degree Of dehydration has also been reported

previously.17 It is speculated that younger children, who can either independently gain access to fluids nor successfully communicate symptoms, experience a greater degree of

dehydration and acidosis.18 19 despite reports that severe dehydration is rare in

DKA,1 4 5 severe dehydration was observed in 18/42 (43%)Patients in this study, a higher proportion than recorded in he studies of Harris et al 7 (23.7%) and Fagan et al 4 (12%). Over Hydration In Diabetic Ketoacidosis Essay.

This difference could be due to different patient demographics, Such as the large geographical size of our referralegion and subsequent delays in transport for definitive treatment.16

Table 3

Comparison of vital signs, serum markers and demographics between those with mild, moderate

and severe dehydration*

Non-severe dehydration (n=24) Severe dehydration (n=18) p Value

Age (years)

11.5 (7–15)

Duration of symptoms (days

6 (3–28)

Length of stay (h)

30 (24–48)

PCCU admission (%

New diabetes (%)

Delta heart rate mean (bpm

HbA1c (%)

pH

HCO3 (mmol/l)

Anion gap corrected

Glucose (mmol/l)

Blood urea nitrogen (mmol/l)

Cr (μmol/l)

Lactate (mmol/l)

Na+ (mmol/l)

Na+ corrected (mmol/l)

Osmolality (mOsm/kg)

Osmolar gap (m0sm/kg)

Fluid (ml/kg/12 h)

Fluid over the calculated maintenance (%)

Values are median (25th–75th centiles).

*Dehydration was subcategorized based on change in body weight during diabetic ketoacidosis (severe: >6% in children,

>10% in infants).

AG, anion gap; PCCU, pediatric critical care unit. Over Hydration In Diabetic Ketoacidosis Essay.