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Abstract

Aim:

The aim of this study was to determine some endocrinological and biochemical changes of scorpionism in children in Upper Egypt. In addition, it aimed to find any possible relationship between these changes and the severity of scorpionism.

Patients and methods:

The present study was carried out at two university hospitals in Upper Egypt and included 42 children with envenomation and 20 apparently healthy children as controls. In all subjects, levels were measured of noradrenaline, aldosterone, insulin and cortisol, and some biochemical parameters and electrolytes including nitric oxide (NO), creatine phosphokinase (CPK), Na+ and K+.

Results:

Na+, NO and CPK levels were significantly higher in children with envenomation compared with the controls. Also, there was a significant reduction in K+ in patients compared with controls. Children with severe envenomation had significantly higher levels of noradrenaline, cortisol and aldosterone compared with the controls and mild cases. However, insulin levels were significantly decreased in severe cases of scorpionism compared with mild ones. Moreover, hyperglycemia was detected in all patients with envenomation compared with controls, with significantly higher blood glucose levels among children with severe envenomation compared with mild cases.

Conclusion:

Endocrinological changes were common in all children with scorpion envenomation and more obvious in cases of severe envenomation. The released mediators may account for several inflammatory manifestations such as pulmonary edema, myocardial failure, systemic inflammatory response syndrome and multiple organ failure. The use of insulin is recommended in cases of severe envenomation to improve the outcome.

Keywords

aldosterone hyperglycemia insulin nitric oxide noradrenaline scorpion envenomation

Introduction

Scorpionism is common in tropical and subtropical regions. It is considered an acute life-threatening medical emergency among the rural population in most places. In our locality, Upper Egypt, scorpions still represent a medical problem and a life hazard, especially to children [Elston, 2003; Mohamad et al. 2014]. Death due to severe scorpion envenoming syndrome is a common event in the developing countries. The symptoms and signs of envenomation are usually more severe in children, especially younger ones [Bahloul et al. 2010]. The clinical manifestations of scorpionism are due to complex interactions between sympathetic and parasympathetic stimulation [Mohamad et al. 2014; Bahloul et al. 2010]. This leads to increased release of neurotransmitters and mediators, resulting in a cascade of pathological events, involving the nervous system, the cardiovascular and the respiratory system, eventually leading to death [Gueron et al. 1992b; Ismail, 1995; Possani et al. 1999]. Scorpionism results in hormonal and biochemical changes with significant release of catecholamines, increased angiotensin II and inhibition of insulin secretion [Gueron et al. 1992b; Ismail, 1995]. Increased sympathetic activity causes increased renin release by stimulation of the juxtaglomerular system. The subsequent increase in angiotensin secretion boosts the sympathetic nerve output by direct action on the brainstem and by reducing baroreceptor mechanisms. Thus, the renin–angiotensin system is a significant facilitator of sympathoadrenal traffic in scorpionism [Radha Krishna Murthy and Vakil, 1988a; Grange, 1977]. Envenomation by scorpions involves the activation of the inflammatory response with the release and activation of proinflammatory cytokines and other mediators, such as nitric oxide (NO) [Petricevich, 2010]. NO plays a crucial role in the regulation of vascular tone and organ blood flow, as well as the inhibition of platelets and neutrophil aggregation. However, excessive production of NO has been reported in several myocardial disorders involving inflammatory process, such as endotoxic shock and heart failure. Systemic inflammatory response that is associated with increased NO production may contribute to hypotension, vascular hyporeactivity, and multiple organ failure in patients with scorpionism [Sahan-Firat et al. 2012]. The aim of this study was to determine the endocrinological and biochemical changes in children with scorpionism in Upper Egypt. In addition, we aimed to find any possible relationship between these changes and the severity of scorpionism.

Patients and methods

Patients

This study was carried out at two university hospitals, South Valley University and Assiut University, during the summer months from May to October 2014 after approval from Qena Faculty of Medicine Ethical Committee. The study included 42 children with scorpion envenomation admitted to the emergency unit of South Valley University and Assiut University hospitals. Their ages ranged from 1 to 13 years old. Also included were 20 apparently healthy children of matched age and sex who were considered as a control group. Any patient with a previous history of liver, renal or heart disease was excluded from the study. All the children with envenomation were subjected to complete medical history and physical examination. The history included age, locality, time of the sting, site of the sting, time to start of treatment, previous antivenin therapy at the locality and presentation. The patients were classified at baseline into two main groups according to the degree of severity of envenomation, either mild or severe according to the absence or presence of systemic manifestations [Bahloul et al. 2005, 2010]. Group I consisted of 22 children with mild envenomation. They presented with local signs, including local pain, erythema and paresthesia restricted to the sting area. They were admitted and treated at the emergency unit of our hospitals. Group II consisted of 20 children with severe envenomation. They presented with systemic manifestations such as cardiovascular, respiratory or neurological symptoms, including cardiogenic shock, pulmonary edema, altered consciousness and convulsion [Mohamad et al. 2014; Bahloul et al. 2005, 2010].

The strategy of our hospitals is to hospitalize all children with scorpionism for observation. All patients in our study were admitted. On admission, all patients received scorpion antivenin together with antihistamine and corticosteroid. Patients with no systemic manifestations were sent to the intermediate care unit for observation. Patients with severe envenomation were transferred to the intensive care unit. Inotropic medications and mechanical ventilation were given if indicated.

Biochemical investigations

The routine laboratory investigations were done for all the studied patients, including blood glucose, urea, creatinine, creatine phosphokinase (CPK), chest X-ray and electrocardiogram and blood gases when indicated. The enzyme-linked immunosorbent assay (ELISA) method was used to determine plasma levels of hormones by commercially available kits: noradrenaline using the Cat Combi ELISA kit (Immuno Biological Laboratories IBL, Hamburg, Germany), Plasma cortisol was measured using a cortisol ELISA kit from Oxford Biomedical Research, USA (catalog no. EA65), and insulin using the UBI-MAGIWE ELISA insulin quantitative kit from UBI United bioreseach inc. USA. Aldosterone was measured by a radioimmunoassay method using the DPC Coat-a-Count™ aldosterone kit; Diagnostic Products Corp. USA. NO level was determined by Griess reagent using a spectrophotometric method (Calbiochem® Nitric Oxide Assay Kit 482650-1KTT, EMD Millipore, Germany). Plasma levels of Na+ and K+ were determined by flame absorption photometer Jenway-PFP7 (Bibby Scientific Limited OSA, UK).

Statistical analysis

The results were statistically analyzed using the computer database Prism program. Data comparisons were performed using the Student t test. The levels of significance were accepted with p less than 0.05, and the results were presented in tables as mean ± standard error.

Results

Table 1 summarizes the epidemiological characteristics of children stung by scorpions. The incidence was higher in those aged more than 6 years (62%), while the lowest was in those less than 2 years (4.7%). Male children were more affected than female children. More patients were from rural areas, the site of the sting was more commonly in lower extremities than other sites, and the time of the sting was more often at night. The death rate was 19% of total cases, all of which were severe cases. A review of the therapeutic measures showed that 17 patients received inotropic medications during their course of treatment and 11 cases were mechanically ventilated. All these patients belonged to the severe group. Table 2 shows various clinical variables among the studied cases. All patients had local pain and sweating (100%), followed by hyperemia, vomiting, tachycardia and irritability (83.3%, 81%, 81% and 73.3% respectively). Table 3 shows the levels of the studied biochemical parameters in children with mild and severe envenomation in comparison to controls. Na+, NO and CPK levels were significantly higher in patients than controls. K+ was significantly lower in patients than controls. Table 4 shows the levels of the studied hormonal parameters in children with mild and severe envenomation in comparison to controls. Levels of noradrenalin, cortisol and aldosterone were significantly higher in children with scorpion envenomation than controls, and in severe cases compared with mild ones. However, insulin levels were significantly lower in severe cases of scorpion envenomation than mild ones. Moreover, we found hyperglycemia in all patients compared with controls, with higher significance in severe cases compared with mild cases.

Table 1.

Epidemiological characteristics of children with scorpion sting.

Epidemiological characteristics		Number of patients, n = 42	%
Age (years)	<2	2	4.7
	2–6	14	33.3
	>6	26	62
Sex	Male	25	56.8
Sex	Female	17	43.2
District	Rural	37	84
District	Urban	5	16
Sting site	Lower extremity	24	54.5
	Upper extremity	13	30.9
	Unknown	5	14.6
Time of sting	Night	31	73.8
Time of sting	Day	11	26.2
Envenomation severity	Mild	22	52.4
Envenomation severity	Severe	20	47.6
Outcome	Recovery	34	81
	Death	8	19

Table 2.

Various clinical variables among the studied cases.

Clinical variables*		Number of patients, n = 42	%
Local signs	Pain	42	100
	Hyperemia	35	83.3
	Itching	7	16.6
	Swelling	3	7
Neurological manifestations	Irritability	31	73.8
	Hypothermia	9	21.4
	Hyperthermia	13	31
	Sweating	42	100
	Convulsion	7	16.6
	Coma	4	9.5
	Myosis	2	4.8
Cardiovascular manifestations	Tachycardia	34	81
	Bradycardia	8	19
	Hypotension	7	16.6
	Hypertension	23	54.7
Gastrointestinal manifestations	Vomiting	34	81
	Abdominal pain	18	42.8
	Diarrhea	6	14.2
	Hypersialorrhea	5	12
	Distension	3	7
Respiratory manifestations	Bradypnea	9	21.4
	Tachypnea	22	52.3
	Bronchial congestion	7	16.6
	Acute pulmonary edema	8	19
Genitourinary system	Priapism	3	7
	Oliguria	11	26
	Hematuria	2	4.8

Categories are not mutually exclusive.

Table 3.

Biochemical parameters in children with mild and severe envenomation in comparison to controls.

Chemical parameters	Children with envenomation n = 42		Controls (III) n = 20	p values
Chemical parameters	Mild cases (I) n = 22	Severe cases (II) n = 20	Controls (III) n = 20	I versus II	I versus III	II versus III
Glucose (mmol/liter)	9.7±2.1	17.1±3.4	6.8±0.5	<0.001	<0.001	<0.001
NO (M/liter)	121 ±17	101±1	54±6.4	NS	<0.001	<0.05
CPK (IU/liter)	440.8±30.1	620.7±40.5	157.9±22.3	<0.001	<0.001	<0.001
Na+ (nmol/liter)	158 ±37	148 ±29	142 ±33	<0.05	<0.05	NS
K+ (nmol/liter)	2.8 ± 0.06	5.39 ±2.3	5.49 ±2.5	<0.05	<0.05	NS

Results are expressed as mean ± standard error. T test used unpaired t test, two tailed.

CPK, creatine phosphokinase; NO, nitric oxide; NS, nonsignificant.

Table 4.

The levels of some hormonal parameters in children with mild and severe envenomation in comparison to controls.

Chemical parameters	Children with envenomation n= 42		Controls (III) n = 20	p values
Chemical parameters	Mild cases (I) n = 22	Severe cases (II) n= 20		I versus II	I versus III	II versus III
Noradrenaline (ng/ml)	0.60 ± 0.05	0.88 ± 0.06	0.45 ± 0.04	<0.001	NS	<0.001
Aldosterone (ng/dl)	16.5 ± 3.3	28.3 ± 4.9	7.4 ± 0.46	<0.05	<0.001	<0.05
Cortisol (nmol/liter)	288.36 ± 53.09	680.70 ± 131.33	247.10 ± 49.17	<0.05	<0.001	<0.001
Insulin (µu/ml)	8.40 ± 0.58	7.91 ± 0.79	8.72 ± 0.44	<0.05	NS	<0.001

Results are expressed as mean ± standard error. T test used unpaired t test, two tailed.

NS, nonsignificant.

Discussion

The scorpion is a common medical, public health problem and a life-threatening hazard in many areas of the world [Mohamad et al. 2014; Mullen and Stockwell, 2002; Theakston et al. 2003]. The venom distribution in the extravascular compartment is fast, explaining the early appearance of the symptoms [Bahloul et al. 2005, 2010]. Death due to scorpionism is a common event, especially in children. It was reported that severe scorpionism causes an autonomic storm resulting in a massive release of catecholamines, angiotensin II, glucagon, cortisol and changes in insulin secretion. This results in a syndrome of energy insufficiencies of the vital organs, which causes myocardial damage, cardiovascular disturbances, peripheral circulatory failure, pulmonary edema and many other clinical manifestations, either single or in combination, producing multisystem organ failure and death. It seems possible that scorpion envenomation is one of the noninfectious processes that can result in systemic inflammatory response syndrome, which can lead to multiorgan failure [Nouira et al. 2007; Chippaux and Goyffon, 2008; Krifi et al. 1998; Nunan et al. 2003; Murthy, 2000; Pessini et al. 2003; Adiguzel et al. 2007].

In our study the frequency of severe envenomation was higher in children less than 2 years old (Table 1); this may be attributed to their small body mass, a proportionately greater number of stings to the head, neck and body, and their poor withdrawal reflex when suffering a sting. This latter factor gives the scorpion a chance to inject more venom and to inflict multiple stings. Moreover, the higher frequency of severe scorpion envenomation in children may be due to rapid toxin absorption, extensive distribution from blood to tissues and slower elimination from children compared with adults [Hisham, 1997; Nunan et al. 2004].

Regarding hormonal changes, all our children with envenomation showed significant elevation of circulating levels of noradrenaline and cortisol in comparison to controls. Moreover, children with severe envenomation showed significantly higher mean values of noradrenaline and cortisol than mild cases (Table 4); this is in accordance with other researchers [Osnaya-Romero et al. 2001].

In our study, we found increased serum levels of aldosterone in all children with scorpion envenomation compared with controls, with higher significance in severe cases than in mild cases (Table 4). This is in agreement with previous researchers [Gueron et al. 1992a]. A total of 54.7% of our patients had high blood pressure (Table 2). The increased circulating catecholamines following scorpion envenomation and sympathetically induced renin release may play an important role in the pathogenesis of hypertension.

As regards insulin levels, patients with severe scorpionism had decreased insulin levels compared with mild cases (Table 4). Moreover, we found hyperglycemia in all cases compared with controls, with higher significance in severe cases than mild cases (Table 3). These results are in agreement with previous reports [Radha Krishna Murthy and Vakil, 1988a, 1988b]. Hyperglycemia could be due to a massive release of catecholamines, glucagon, cortisol, changes in thyroid hormone levels and in insulin secretion [Radha Krishna Murthy and Vakil, 1988a; Murthy, 2000; Gueron et al. 1992a.

The serum levels of NO in all patients were significantly elevated compared with controls and were significantly more elevated in severe cases than mild cases (Table 3). These findings are in line with other investigators who found a significant higher mean level of NO in all children with envenomation, both severe and mild cases, in comparison to controls. That elevation was positively correlated with the severity of envenomation [Prasad and Bharadwaj, 1996]. NO elevation may be due to the effect of released cytokines on the activation of the inducible isoform of NO synthase enzyme on L-arginine amino acid on the endothelial cells. Since NO is considered as a mediator of acetylcholine action, further synthesis of NO leads to such hypotension [Prasad and Bharadwaj, 1996], which was detected in 16.6% of our patients (Table 2).

Regarding electrolyte disturbances, we found increased serum sodium and decreased serum potassium in cases compared with controls (Table 3). Generally, it was suggested that electrolyte disturbances are due to the release of various mediators such as catecholamines, which directly affect Na+/K+ adenosine triphosphate and cellular K+ distribution [Murthy, 2000]. The case fatality rate recorded in the present study was 19%. This result is much higher than that reported by other investigators [Meki et al. 2003; Mekki and Mohey El-dean, 1998]. Most deaths were secondary to respiratory or cardiovascular failure.

Conclusion

Endocrinological changes were common in children with scorpion envenomation and more obvious in cases of severe envenomation compared with mild cases. The hormonal and biochemical mediators affecting inflammatory processes that were released after scorpion envenomation were noradrenaline, cortisol, aldosterone and NO. These released mediators may account for several of the inflammatory manifestations observed, such as pulmonary edema, myocardial failure, systemic inflammatory response syndrome and multiple organ failure.

Recommendation

Most of the complications and deaths in children with scorpion envenomation are preventable. The main preventable factors include the inability to recognize early the severity of the envenomation and delay in referring victims to specific healthcare facilities. Hospital-related preventable factors in endemic areas include inadequate skills and lack of intensive care units. In addition, delay in seeking emergent treatment contributes to most rural deaths. So, heath authorities must recognize the importance of the problem and the need for emergent intervention, and strengthen the primary healthcare system at the district and subdistrict levels to provide adequate medical services. The use of insulin is recommended in cases of severe envenomation to improve the outcome. Rapid evaluation of the severity of the envenomation, mainly in children, is essential to establish the prognosis and administer adequate treatment.

Footnotes

Acknowledgements

The Ethical Committee of Qena Faculty of Medicine, South Valley University, Egypt approved the study. All methods and procedures used in this study were approved by the Institutional Review Board at Assiut University, Egypt. Informed consent followed the guidelines set forth by the Institutional Review Board at Qena University and included a brief description of study procedures, potential benefits, a discussion of the voluntary nature of the study, right to withdraw without consequences, and confidentiality of information. Informed consents were written in Arabic language that was age appropriate for all participants in the study. Prior to participation in the study, parents were required to give consent for participation. Finally, participants were given a Participant’s Bill of Rights.

All authors have read and agreed with the content of this study and no portion of this work has been published previously or is under consideration for publication elsewhere and is an original article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

References

Adiguzel

Ozkan

Inceoglu

(2007) Epidemiological and clinical characteristics of scorpionism in children in Sanliurfa, Turkey. Toxicon 49: 875–880.

Bahloul

Chabchoub

Chaari

Chtara

Kallel

Dammak

(2010) Scorpion envenomation among children: clinical manifestations and outcome (analysis of 685 cases). Am J Trop Med Hyg 83: 1084–1092.

Bahloul

Rekik

Chabchoub

Chaari

Ksibi

Kallel

(2005) Neurological complications secondary to severe scorpion envenomation. Med Sci Monit 11: CR196–CR202.

Chippaux

Goyffon

(2008) Epidemiology of scorpionism: a global appraisal. Acta Tropica 107: 71–79.

Elston

(2003) Life-threatening stings, bites, infestations, and parasitic diseases. Clin Dermatol 41: 367–375.

Grange

(1977) Elevation of blood pressure and plasma renin levels by venom from scorpions, Centruroides sculpturatus and Leiurius quinquestriatus. Toxicon 15: 429–433.

Gueron

Ilia

Shahak

Sofer

(1992a) Renin and aldosterone levels and hypertension following envenomation in humans by the yellow scorpion Leiurus quinquestriatus. Toxicon 30: 765–767.

Gueron

Ilia

Sofer

(1992b) The cardiovascular system after scorpion envenomation, a review. Clin Toxicol J 30: 245–258.

Hisham

(1997) Scorpion sting syndrome: epidemiology, clinical presentation and management of 2240 cases. East Mediterr Health J 3: 82–99.

10.

Ismail

(1995) The scorpion envenoming syndrome. Toxicon 33: 825–858.

11.

Krifi

Kharrat

Zghal

Abdouli

Abroug

Bouchoucha

(1998) Development of an ELISA for the detection of scorpion venoms in sera of humans envenomed by AAG and BOT: correlation with clinical severity of envenoming in Tunisia. Toxicon 36: 887–900.

12.

Meki

Hasan

El-Deen

Bakkar

(2003) Dysregulation of apoptosis in scorpion envenomed children: its reflection on their outcome. Toxicon 42: 229–237.

13.

Mekki

Mohey El-dean

(1998) Serum interleukin-1b, interleukin-6, nitric oxide and a1-antitrypsin in scorpion envenomed children. Toxicon 36: 1851–1859.

14.

Mohamad

Elsayh

Mohammad

Saad

Zahran

Abdallah

(2014) Clinical characteristics and outcome of children stung by scorpion. Eur J Pediatr 173: 815–818.

15.

Mullen

Stockwell

(2002) Scorpions (Scorpiones). Med Vet Entomol 20: 411–423.

16.

Murthy

(2000) The scorpion envenoming syndrome: a different perspective. The physiological basis of the role of insulin in scorpion envenoming. Review article. J Venom Anim Toxins 6: 4–51.

17.

Nouira

Boukef

Nciri

Haguiga

Elatrous

Besbes

(2007) A clinical score predicting the need for hospitalization in scorpion envenomation. Am J Emerg Med 25: 414–419.

18.

Nunan

Arya

Hochhaus

Cardoso

Moraes-Santos

(2004) Age effects on the pharmacokinetics of tityustoxin from Tityus serrulatus scorpion venom in rats. Braz J Med Biol Res 37: 385–390.

19.

Nunan

Moraes

Cardoso

Moraes-Santos

(2003) Effect of age on body distribution of Tityustoxin from Tityus serrulatus scorpion venom in rats. Life Sci 73: 319–325.

20.

Osnaya-Romero

de Jesus Medina-Hernández

Flores-Hernández

León-Rojas

(2001) Clinical symptoms observed in children envenomated by scorpion stings, at the children’s hospital from the State of Morelos, Mexico. Toxicon 39: 781–785.

21.

Pessini

de Souza

Faccioli

Gregório

Arantes

(2003) Time course of acute-phase response induced by Tityus serrulatus venom and TsTX-I in mice. Int Immunopharmacol 3: 765–774.

22.

Petricevich

(2010) Scorpion venom and the inflammatory response. Mediators Inflamm 2010: 903295.

23.

Possani

Becerril

Delepierre

Tytgat

(1999) Scorpion toxins specific for Na+-channels. Eur J Biochem 264: 287–300.

24.

Prasad

Bharadwaj

(1996) Hydroxyl radical – a mediator of acetylcholine-induced vascular relaxation. J Mol Cell Cardiol 28: 2033–2041.

25.

Radha Krishna Murthy

Vakil

(1988a) Elevation of plasma angiotensin levels in dogs by Indian red scorpion (Buthus tamulus) and its reversal by administration of insulin and tolazoline. Indian J Med Res 88: 376–379.

26.

Radha Krishna Murthy

Vakil

Yeolekar

Vakil

(1988b) Reversal of metabolic and electrocardiographic changes induced by Indian red scorpion (Buthus tamulus) venom by administration of insulin, alpha-blocker and sodium bicarbonate. Indian J Med Res 88: 450–457.

27.

Sahan-Firat

Canacankatan

Korkmaz

Yildirim

Tamer

(2012) Increased production of nitric oxide mediates selective organ-specific effects of endotoxin on oxidative stress. Antiinflamm Antiallergy Agents Med Chem 11: 161–172.

28.

Theakston

Warrell

Griffiths

(2003) Report of a WHO workshop on the standardization and control of antivenoms. Toxicon 41: 541–557.

Endocrinological and biochemical changes of scorpionism in children in Upper Egypt

Abstract

Aim:

Patients and methods:

Results:

Conclusion:

Keywords

Introduction

Patients and methods

Patients

Biochemical investigations

Statistical analysis

Results

Discussion

Conclusion

Recommendation

Footnotes

Acknowledgements

Funding

Declaration of Conflicting Interests

References