|Year : 2019 | Volume
| Issue : 2 | Page : 47-54
Outcome of hyperglycemic emergencies in a tertiary hospital, South East, Nigeria
Marcellinus O Nkpozi1, Ignatius U Ezeani1, Ibitrokoemi F Korubo2, Sunny Chinenye2, Assumpta U Chapp-Jumbo3
1 Department of Internal Medicine, Federal Medical Centre, Umuahia, Nigeria
2 Department of Medicine, Endocrinology, Diabetes and Metabolism Unit, University of Port Harcourt Teaching Hospital, Port Harcourt, Nigeria
3 Department of Paediatrics, Abia State University Teaching Hospital, Aba, Nigeria
|Date of Submission||31-Oct-2017|
|Date of Acceptance||08-Mar-2018|
|Date of Web Publication||20-Jun-2019|
Dr. Marcellinus O Nkpozi
Department of Internal Medicine, Diabetes and Metabolism Unit, Federal Medical Centre, Umuahia
Background: Hyperglycemic emergency (HE) is typically represented by diabetic ketoacidosis, (DKA) and hyperosmolar hyperglycemic state (HHS). It is a common cause of hospitalization due to diabetes mellitus (DM) and is associated with considerable mortality. In South East Nigeria, there is a paucity of studies on the treatment outcome of HE, hence the need for this study. Objective: The aim and objective of the study were to determine the outcome of treatment of adult persons living with diabetes managed for HE at Federal Medical Centre (FMC), Umuahia. Materials and Methods: This was a prospective study in which 110 consecutive adult patients managed for HE at FMC, Umuahia, were recruited. Data obtained included a total number of medical and diabetic admissions within the study period. For participants that met the inclusion criteria for the study, their bio-data, blood pressures, level of consciousness at presentation or while being treated, random plasma glucose, plasma electrolytes, urea, creatinine, and plasma 3-beta-hydroxybutyrate were noted and/or measured. Similarly, urine sample was collected from each participant for analysis (glucose, protein, and ketone). The outcome measures were patient's survival, hospitalization duration, and death. Analysis of data was done using SPSS 20.0 and the level of statistical significance was set at P < 0.05. Results: Of the 110 participants recruited, there were 46 (41.8%) males and 64 (58.2%) females. HE constituted 15.6% of the total medical admissions within the study period with a mortality of 10%. DKA and mixed form of HE were the predominant patterns in the study. While hospitalization duration was variable, no female participant was discharged against medical advice. Conclusion: The study showed that HE is a frequent acute complication of DM in this region of Nigeria and that HE typically presents as DKA and mixed form. Hospitalization for HE had a variable duration with a significant mortality.
Keywords: Diabetic ketoacidosis, hyperglycemic emergency, hyperosmolar hyperglycemic state, treatment outcome
|How to cite this article:|
Nkpozi MO, Ezeani IU, Korubo IF, Chinenye S, Chapp-Jumbo AU. Outcome of hyperglycemic emergencies in a tertiary hospital, South East, Nigeria. Sahel Med J 2019;22:47-54
|How to cite this URL:|
Nkpozi MO, Ezeani IU, Korubo IF, Chinenye S, Chapp-Jumbo AU. Outcome of hyperglycemic emergencies in a tertiary hospital, South East, Nigeria. Sahel Med J [serial online] 2019 [cited 2019 Jul 22];22:47-54. Available from: http://www.smjonline.org/text.asp?2019/22/2/47/260843
| Introduction|| |
Complications of diabetes mellitus (DM) can be acute or chronic. Hypoglycemia and the hyperglycaemic emergencies (HE) constitute the acute metabolic complications of DM. HE is typically represented by diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS). HHS and DKA result from relative or absolute insulin deficiency, respectively, and constitute a spectrum of emergencies caused by poor glycemic control. HEs are associated with significant morbidity and mortality.
Globally, mortality rate of HHS ranges from 10% to 50% which is considerably higher than that of DKA, which is 1.2%–9%. In a study in Benin city, Nigeria, it was noted that the most common type of HE was HHS and that mortality was also highest with HHS. In tertiary hospital-based studies in Southern Nigeria, the most common DM-related indications, for hospital admissions were HHS, DKA, and diabetic foot ulcers. Similarly, in another tertiary hospital-based study in North West, Nigeria, sepsis (30.9%), HHS (14.2%), DKA (7.4%), diabetic foot ulcers (7.4%), and cerebrovascular accidents (stroke) were the main indications for diabetes hospital admissions while HE constituted 83% of all DM admissions.
As regards the pathophysiology of DKA,, insulin deficiencies are usually accompanied by increased counter-regulatory hormones such as glucagon, cortisol, catecholamine, and growth hormones. The insulin deficiencies result in increased lipolysis and increased free fatty acids' generation which undergoes beta-oxidation in the liver mitochondria to form ketoacids (3-beta-hydroxybutyrate, acetoacetate, and acetone) resulting to metabolic acidosis. Increased hepatic glycogenolysis, decreased tissue utilization of glucose due to insulin deficiency, and unchecked gluconeogenesis result to hyperglycemia which causes osmotic diuresis. The latter leads to marked dehydration and electrolyte losses. In HHS, the presence of some insulin reserve prevents lipolysis leading to minimal or absent ketogenesis. With decreased fluid intake by the patients who are usually elderly, dehydration is severe in HHS, hence they are predisposed to prerenal acute kidney injury and hyperosmolarity.
Treatment, measures for HE include fluid replacement, insulin therapy, electrolytes replacement, monitoring, correction of hyperosmolarity, identification and treatment of underlying cause (s), and resolution and conversion to home remedies.
In South East Nigeria where this study was carried out, there is a paucity of studies on the treatment outcome of this important acute complication of DM. This study, therefore, set out to bridge that gap in knowledge by assessing the frequency and outcome of HE among diabetic admissions at the Federal Medical Centre (FMC), Umuahia.
| Materials and Methods|| |
Study design and site
This was a prospective observational study conducted at the accident and emergency (A and E) department and medical wards of FMC, Umuahia in Abia state, South East, Nigeria. Umuahia is a metropolitan town with some commercial activities going on in the city. Some study participants were recruited when they sought treatment at the diabetes and medical outpatient clinics. Each recruited participant was admitted, appropriate treatment commenced, and outcome of treatment in the Emergency room and medical wards (well and discharged home, discharged against medical advice, or died) were recorded. From the emergency room and in the medical wards, such patients with a diagnosis of HE (DKA and HHS, etc.,) were managed using the local treatment protocol of the Department of Internal Medicine, FMC, Umuahia [Appendix 1]. The study was approved by the Health Research Ethics Committee (HREC) of Federal Medical Centre, Umuahia, Abia State, Nigeria with protocol number FMC/QEH/G.596/Vol.10/109 dated 20th May 2014.
Written informed consent was obtained from all patients recruited into the study as soon as their clinical/mental state became stable enough to take their decisions on whether or not to participate in the study. The study participants, also, signed a written informed consent for sharing the study data for publication purposes.
It is important to note that all the procedures involved in the study which lasted between July 2015 to March 2016 have been carried out as per the guidelines given in Declaration of Helsinki 2013.
Sample size and sampling
The sample size was calculated using appropriate formula based on the incidence rate of HE of 12% recorded in Iddo Ekiti. Participants who consented to the study were consecutively recruited.
Inclusion and exclusion criteria
Persons living with diabetes and new-onset diabetes aged 18 years and above with a diagnosis of HE (see definitions of operational terms below) admitted through the A and E unit, diabetes clinic, or medical outpatient clinic were included in the study. Patients diagnosed with HE which started while in the Intensive Care Unit, surgical, medical, and obstetric/gynecological wards were also recruited. However, patients who declined consent when they became stable/conscious and those who had coexisting congestive heart failure, end-stage renal disease, or other major organ failures were excluded from the study.
Recruitment and data collection
From July 2015 to March 2016, using the consecutive type of nonprobability sampling technique. One hundred and twenty-three accessible participants that met the diagnostic criteria for HE on presentation at FMC, Umuahia, were intended to constitute the sample population. Of these, five died few hours after admission in A and E before being investigated, 3 were <18 years, 5 refused to give informed consent, and 110 participants were recruited, having met the inclusion criteria.
Data for the study were obtained from two sources:
- Data extracted from patients' case notes, ward admission/discharge register and death certificates included total number of medical and diabetic admissions within the study period, sociodemographic data of the study participants, and their level of consciousness at presentation or while being treated
- Each participant's blood pressure was measured using a mercury sphygmomanometer (Accoson, England) at heart level using appropriate cuff size. Each participant's random plasma glucose was measured using the glucose oxidase method of Trinder, plasma electrolytes were measured using the method of ion-selective electrode, plasma urea was measured using an enzymatic (urease) method, while plasma creatinine was determined by the Jaffe's alkaline picrate kinetic method. Plasma 3-beta-hydroxybutyrate was measured for each participant using an enzymatic (3-hydroxybutyrate dehydrogenase) oxidation of D-3-hydroxybutyrate to acetoacetate. Similarly, urine sample was collected from each subject for analysis (glucose, protein, and ketone) using Combi-10 strips. Plasma osmolality was calculated using 2 × plasma sodium (mmol/L) + plasma glucose (mmol/L) + plasma urea (mmol/L).
The outcome measures were patient's survival, hospitalization duration, and death.
The Statistical Package for the Social Sciences (SPSS Inc., Chicago, IL, USA) version 20.0 statistical software was used for data analysis. For continuous variables such as the ages and duration of hospital stay of the study participants, mean values and standard deviations (SD) were calculated and the means compared using two-sample t-test. Categorical variables such as frequency of DKA, HHS, and mixed form among diabetic hospital admissions, sex, and outcome of HE were summarized using proportions expressed in percentages. The categorical variables were compared using the nonparametric test Chi-square test. The level of statistical significance was set at P < 0.05.
Definitions of operational terms
- Type 1 DM patients were diabetic patients, typically diagnosed before age 30, who required insulin injection for survival from the time of diagnosis. Type 1 DM could present at any age due to variability in the rate of beta cell destruction
- Type 2 DM patients were patients who were not dependent on insulin for survival from the time of diagnosis; such patients were surviving on diet, lifestyle modifications, and glucose-lowering drugs but may require insulin for control of hyperglycemia
- New onset diabetes was persons diagnosed with diabetes on the present admission
- HE – a medical emergency in which a person living with diabetes or new onset diabetes had symptoms of acute metabolic decompensations, was dehydrated (hypovolemia), had random plasma glucose of ≥300 mg/dl with or without impaired mental status, and required immediate intravenous fluid and soluble insulin for resuscitation
- DKA was a biochemical diagnosis in which plasma glucose ≥300 mg/dl, ketonuria ≥2+, normal plasma osmolality, and HCO3<15 mmol/L
- HHS – also a biochemical diagnosis in which plasma glucose was ≥500 mg/dl, plasma osmolality ≥320 mosmol/kg, had absent or minimal ketonuria and plasma HCO3>15 mmol/L, and altered mental status due to hyperosmolality
- Normo-osmolar nonketotic hyperglycemic state (NNKHS) – plasma glucose ≥300 mg/dl, normal plasma osmolality 270–290 mosmol/kg with nil or minimal ketonemia/ketonuria
- Mixed or indeterminate form had features of DKA and HHS at the same time thus HCO3<15 mmol/L, plasma osmolality ≥320 mosmol/kg with ketonuria ≥2+ or vice versa.
| Results|| |
Of the 705 patients admitted into the medical wards (male and female) through the medical outpatient clinics and A and E unit of FMC, Umuahia, within the study period of July 2015 to March 2016, 135 of them (19.15%) had complications (acute and chronic) of DM necessitating hospitalization. The 110 participants who met the inclusion criteria for this study constituted 15.6% of the total medical admissions and 81.5% of the DM-related complications within the period. Three of the study participants (2.7%) had Type 1 DM while 107 (97.3%) had Type 2 DM. A total of 46 males and 64 females participated in the study with a male–female ratio of 1:1.4; age ranged from 18 to 90 years and mean age was 58.10 ± 15.03 years. There was no statistically significant difference between the mean ages of male and female participants (60.9 ± 15.1 versus 56.1 ± 14.8, respectively, t = 1.692, P = 0.73).
While more than half of the study participants (56 [50.9%]) had the mixed or indeterminate form of HE, 44 (40%) had DKA, 6 (5.5%) had NNKHS, and only 4 (3.6%) had HHS as shown in [Table 1].
|Table 1: Patterns of hyperglycaemic emergency in Federal Medical Centre, Umuahia|
Click here to view
[Table 2] shows that, while 91 of the participants (82.7%) were discharged home well, 11 (10%) died and 8 (7.3%) were discharged against medical advice. The participants that died had the least mean duration of hospitalization (9 days), while those that were discharged home well had the longest mean duration of hospitalization (20.9 days).
|Table 2: Outcome and patterns of hyperglycemic emergencies at Federal Medical Centre, Umuahia|
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The duration of hospitalization of the participants ranged from 3 to 105 days with a mean (SD) duration of hospital stay at 18.96 ± 21.69 days. The mean (SD) duration of hospital stay for the females, 21.06 ± 23.86, was more than that of the males, 16.04 ± 18.11. There was no statistically significant difference between the mean duration of hospitalization of male and female participants (P = 0.233). Mortality among the participants was highest in the mixed or indeterminate form (4 [3.6%]) followed by DKA and NNKHS each (3 [2.7%]) and least in the participants with HHS (0.9%).
Of the 11 participants that died, majority (63.6%) were males and all the participants who were discharged against medical advice were males too; none of the female participants was discharged against medical advice. These differences in the outcome of HE noted between the males and females were statistically significant (χ2 = 15.53, P = 0.001) as shown in [Table 3].
|Table 3: Relationship between gender of participants and outcome of hospitalization|
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| Discussion|| |
The main findings of this study were that HEs constituted 15.6% of the total medical admissions within the study period, DKA and mixed form were the predominant patterns of HE while mortality from HE was 10%.
The finding of HEs accounting for 15.6% of all medical admissions was higher than the 3.6% reported by Okoro et al. Again, the contribution of HE to diabetes-related admissions (81.5%) was higher than the 30% reported by Chijioke et al. in Ilorin, 11.86% by Ajayi and Ajayi 33.3% by Okoro et al., and the 40% reported by Ogbera et al. in Lagos. This figure (81.5%) was similar to the 83% reported by Uloko et al. in North West, Nigeria. This could have been a result of increased health/diabetes awareness and increased diagnosis especially of new-onset DM. The trend could also be in keeping with projected increasing prevalence of Type 2 DM (T2DM) as a result of obesity, sedentary lifestyles, increased urbanization, and westernization. The contribution of HEs to medical admissions (15.6%) in this study was similar to the 15% of all medical admissions reported by Ogbera et al. in Lagos.
The most common form of HEs in this study was DKA and the mixed form. This is comparable to the findings by Nyenwe et al. probably because of increasing occurrence of DKA in T2DM patients, some of whom actually may have had Type 1 DM, but at variance with reports from Benin, where HHS was seen more than DKA. The explanation for this difference could have been from increased diagnosis of DKA in this study arising from simultaneous check of urine ketone and plasma 3-beta-hydroxybutyrate in the participants. Use of plasma 3-beta-hydroxybutyrate to define ketonemia in the index study was an improvement over previous studies in Nigeria.,, The preponderance of mixed or indeterminate form of HE in this study could just be a reflection of the fact that HE represents a spectrum of clinical conditions which could overlap.
While death from HE occurred in 10% of the participants, most of the participants (82.7%) were discharged home well. This mortality rate was higher than the 4.8%, and 3.57% reported from Benin,, 0%–2.4% documented in Peru and some western countries, 4.8% reported by MacIsaac et al., and similar rates in South African. The explanation is not clear but probably due to circumstances surrounding their presentations to the A and E department and death arising from the other comorbid conditions. Most deaths recorded in this study may not have been from the metabolic abnormalities associated with HEs as reflected by a mean duration of hospital stay (9 ± 6.5 days) for the study participants that died.
On the other hand, mortality rate in this study was lower than 18.8% and 16% reported by Adesina et al., respectively, 18% by Ogbera et al., 27.7% by Eregie and Unadike in Benin, 25%–33% in some previous studies in East Africa,, and 30%–44% from Sub-Saharan Africa and Asia.,,,, This could have been because of improved laboratory support services as important analytes such as plasma potassium, electrolytes, urea, creatinine, and beta-hydroxybutyrate are now obtainable in a shorter time than before and the diabetes care team was involved early in the management of most cases of HEs.
It is important to note that mortality rate of DKA in a study in Syria at 11.3% and Uyo at 10.3% were similar to that of HEs obtained in this study; the latter probably because of their proximity to each other, similarity of the health-seeking behavior of the populations involved and possibly similar precipitating factors for HE.
Discharge of study participants against medical advice, another outcome measure in this study, was seen mainly among participants that had DKA and indeterminate form of HE who, also, constituted the majority of the participants. It was found in 7.2% of the participants, and this was higher than 3.57% reported by Edo in Benin. Mean duration of hospitalization for the participants discharged against medical advice (11 ± 4.1 days) was comparable to the 12 days reported by Ajayi and Ajayi among diabetes-related admissions. That all the participants who requested for discharge against medical advice (DAMA) in this study were males (and no females) could not be explained easily beyond differences in gender mindsets when facing health challenges. Ezeani et al. in Benin and Ogbera et al. in Lagos, however, did not report any DAMA.
Most of the participants in this study (82.7%) were discharged home well. This finding was comparable to what was found in Lagos where 80% of the participants were discharged home well.
The mean duration and range of days of hospitalization of the participants in this study were 18.96 ± 21.69 and 3–105 days, respectively. This finding was similar to the 24.2 ± 17, with a range of hospital stay of 0.5–88 days by Ezeani et al. and 23 ± 17 with a range of hospital stay of 4–122 days by Ogbera et al. In the index study, dehydration, hyperglycemia, hyperosmolality, metabolic acidosis, and increased anion gap got resolved within the first 1–2 weeks which was similar to the report by Edo in Benin.
Participants who had diabetic foot ulcers, hand or leg ulcers with or without gangrene, and complications had the longest duration of hospital stay. This finding was similar to the findings from studies by Ezeani et al. and Pepper et al., who reported that diabetic foot ulcers were associated with prolonged duration of hospitalization. Many of the diabetic foot ulcers encountered in this study presented late and with gangrene, thereby requiring surgical intervention (amputation) and prolonged period of wound care. Stroke in patients that had HE or comorbid conditions also contributed to the increased duration of hospitalization in this study.
Finally, the mean duration of hospitalization (9 days) for the patients that died in this study was much longer than what was reported by Okoro et al. in Nigeria and Jeanette and Jeremy in Canada where all recorded deaths occurred within 2 days and 48–72 h, respectively. The explanation for this relative long duration of hospitalization for the patients that died could be death from comorbid conditions or precipitating factors and not necessarily from the metabolic abnormalities of HE. The Comorbid factors were not investigated. The contributions of these and precipitating factors to outcome were not determined.
| Conclusion|| |
This study has shown that HE is a major cause of hospitalization in the medical wards; DKA and the mixed forms constituting the main patterns encountered in South East Nigeria. Mortality from HEs is considerable at 10%. Use of 3-beta hydroxyl butyrate measurement to define ketonemia is important in making a diagnosis of DKA. Hospitalization duration is variable and depends on comorbid and/or precipitating conditions. The study has, therefore, served to emphasize the contribution of HEs to morbidity and mortality among medical admissions.
- Nursing and medical officers, Accident and Emergency unit, FMC Umuahia
- Nursing and other medical staff, medical and surgical wards of FMC, Umuahia
- Nkpozi Marcel Kelechukwu for computer services.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| Appendix 1|| |
- Patient is admitted at A and E or medical ward, specimen samples are collected for random plasma glucose, plasma electrolytes, urea creatinine, and urine analysis for protein and ketone
- Fluid replacement with normal saline; rate of replacement being dependent on the degree of dehydration, age, and other associated factors
- Intravenous insulin administration; bolus dose stat and hourly doses till random plasma glucose is ≤250 mg/dl
- Potassium replacement, dose being dependent on plasma potassium concentration which is monitored 2 hourly
- Empirical broad-spectrum antibiotics are used when infection is suspected as a precipitating factor
- Treatment of precipitating factors when identified
- Monitoring – hourly random blood glucose check initially, pulse, BP, respiratory rate, and fluid input/output
- For HHS, prophylactic low-dose enoxaparin is given.
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[Table 1], [Table 2], [Table 3]