Artículo
Epinefrina vs dopamina en el manejo inicial del shock séptico pediátrico
Epinephrine vs dopamine in the initial management of pediatric septic shock
Bethzi Vera Dorado (1)
Editorial
Artículos
Casos Clínicos
(1) Medico Intensivista Pediátrico, Hospital General San Juan de Dios, Oruro, Bolivia. Correspondencia requerida a: Bethzi Vera Dorado, madybeve@gmail.com
REVISTA CIENTÍFICA DEL COLEGIO MÉDICO DE QUILLACOLLO
Periodicidad: Semestral vol. 1, núm. 1, 2022
Recibido el 16 de octubre de 2021. Aceptado para su publicación 20 de enero de 2022
URL: https://colegiomedicodequillacollo.com/
Resumen:
Introducción: El Shock Séptico (SS) es una de las principales causas de mortalidad en pediatría, el uso de fármacos vasoactivos (DAV) debe realizarse precozmente para reducir la mortalidad. Esta investigación pretende comparar la eficacia terapéutica de la Epinefrina vs Dopamina como AVD inicial de niños SS ingresados en la Unidad de Cuidados Intensivos Pediátricos (UCIP) del Hospital Manuel Ascencio Villarroel (HNMAV), hospital de tercer nivel en un País de Renta Media Baja ( PIBM) como Bolivia. Métodos: Se realizó un estudio analítico, prospectivo y longitudinal, se estudiaron niños entre 1 mes a 14 años con diagnóstico de SC; excluyendo pacientes con enfermedades del corazón, enfermedad renal crónica, cáncer, inmunocomprometidos, desnutridos severos o fallecidos antes de iniciar el tratamiento con DAV, o aquellos que requirieron el uso de un segundo DAV. Resultados: Ingresaron al estudio 18 pacientes, 8 para el grupo de dopamina y 10 para el grupo de adrenalina, encontrando diferencias significativas en cuanto a: Categoría de frecuencia cardiaca y para categoría de presión arterial sistólica (p<0.05) tanto para epinefrina como para dopamina, determinando así que existe una relación significativa entre la aplicación del fármaco y estas dos variables. En cuanto a la mortalidad y las relaciones de causa y efecto, se utilizaron las curvas de supervivencia de Kaplan-Meier. Se comparó el uso de dopamina y epinefrina mediante el análisis de Log-Rank de Mantel-Cox, nada de lo que parece haber diferencia entre el uso de dopamina en comparación con epinefrina. Conclusión: Se sugiere que la mortalidad sea la misma con el tratamiento con dopamina o adrenalina; No se observaron efectos adversos con ninguna de las dos terapias.
Palabras clave: Epinefrina, Dopamina, Shock Séptico, Pediatría
Abstract:
Introduction: Septic Shock (SS) is one of the leading causes of mortality in paediatrics, the use of vasoactive drugs (VAD) must be carried out early to reduce mortality. This research pretends to compare the therapeutic efficacy of Epinephrine vs Dopamine as the initial AVD of SS children admitted to the Paediatric Intensive Care Unit (PICU) of the Manuel Ascencio Villarroel Hospital (HNMAV), a third level hospital in a Low Middle Income Country (LMIC) such as Bolivia. Methods: An analytical, prospective and longitudinal study was carried out, children between 1 month to 14 years with a diagnosis of CS were studied; excluding patients with heart disease, chronic kidney disease, cancer, immunocompromised, severely malnourished or deceased before starting treatment with VAD, or those who required the use of a second VAD. Results: 18 patients entered the study, 8 for the dopamine group and 10 for the adrenaline group, finding significant differences regarding: Heart rate category and for systolic blood pressure category (p <0.05) for both epinephrine and dopamine, thus determining that there is a significant relationship between the application of the drug and these two variables. Regarding mortality and cause and effect relationships, Kaplan-Meier survival curves were used. The use of dopamine and epinephrine was compared by means of the Mantel-Cox Log-Rank analysis, nothing that there seems to be a difference between the use of Dopamine compared to epinephrine. Conclusion: Mortality is suggested to be the same with dopamine or adrenaline treatment; No adverse effects were observed with either of the two therapies.
Keywords: Epinephrine, Dopamine, Septic Shock, Paediatric.
About a decade ago, the definitions of sepsis, as well as the diagnostic and therapeutic approach, were evolving due to
the large number of investigations carried out on this subject. Regarding advances in the treatment of septic shock, even in Low Middle Income Countries (LMIC), there is a mortality rate of 25-50%1. Within the physiopathology of septic shock, factors such as: vasodilation, relative and absolute hypovolemia, myocardial dysfunction, increased in the metabolic rate and alteration in both microvascular and regional blood flow, which is why it is necessary to adequately understand the use of inotropic and vasopressors within the resuscitation of the patient with shock due to sepsis to maintain a minimum perfusion pressure and maintain an adequate flow2-4.
One of the first goals in the treatment of critically ill patients is to restore and maintain adequate tissue oxygenation, since tissue hypoxia plays an important role in the development of multiple organ dysfunction, which is a frequent cause of death in the population of critical patients. In recent years, multiple pharmacological agents have been investigated with the aim of improving the evolution of patients with hemodynamic deterioration that is associated with perfusion alterations at the tissue level5,13,14.
The guidelines and recommendations for the campaign on surviving sepsis have described the use of dopamine mainly in adults, not knowing many studies in this regard in children6-10. Currently, the use of dopamine has been left aside in the latest recommendations where the use of adrenaline is suggested even in the absence of a peripheral venous route as an emergency using intraosseous route2,11,12. In this sense This work aims to compare the effect of both drugs with respect to the shorter recovery time and mortality associated with paediatric patients with septic shock.
Methods
An analytical, experimental blind loop, prospective and longitudinal study was carried out. The study subjects were patients admitted to the Paediatric Intensive Care Unit (PICU) of the Manuel A. Villarroel Hospital (HNMAV) from 1 month to 14 years of age with a diagnosis of Septic Shock. A sample was established excluding patients with a diagnosis of septic shock who used drugs other than Dopamine or Adrenaline as the initial drug, heart disease or rhythm disorders, end-stage kidney disease, cancer patients with recent chemotherapy treatment, immunocompromised, acute malnutrition, fluid overload greater than 10% or requiring renal replacement, died before starting treatment with epinephrine or dopamine, treated in another hospital centre.
The assignment of the treatment to start was by simple randomization method, starting with one epinephrine and the next dopamine following the intervention protocol:
Progressive dose of the amine started was increased as follows:
1. Dose A: dopamine 6 mcg / kg / min or epinephrine 0.1mcg / kg / min
2. Dose B: dopamine 8 mcg / kg / min or epinephrine 0.2mcg / kg / min
3. Dose C: dopamine 10 mcg / kg / min or epinephrine 0.3mcg / kg / min
The patient care flow chart is described below, in the investigation.
The variables were categorized and subjected to different analysis routines in Statistical Package for the Social Sciences- SPSS v.22.0.0 for Windows 7. Pairs of variables were related using contingency tables and the Chi-square analysis for these tables. For each pair evaluated, it was determined whether or not there is a significant relationship. On the other hand, for
quantitative evaluations, the response variables were grouped according to the drug used (dopamine or epinephrine) and a Wilcoxon and Mann-Withney U analysis was performed.
The study took as ethical considerations and was bioethical committee approved, the informed consent designed for this purpose, ensuring its voluntary and confidentiality and ensuring risk will be minimal.
Results
A total of 23 patients were obtained, of which 5 were excluded according to the exclusion criteria, leaving the data of 18 patients who were registered and enrolled in the Dopamine and Adrenaline study groups; their behaviour was observed in 6 hemodynamic monitoring variables of the patient with septic shock, finding similar effects in terms of capillary refilling (p=0.807), serum lactate concentration (p=0.233), hourly
diuresis (p=0.490) , Central venous saturation (p=0.060), however, there were differences regarding heart rate (p=0.002) and blood pressure (p=0.025). See table 1
To evaluate the difference in means using the Mann Whitney U test, it was found for the heart rate for the patients to whom dopamine was administered, it ranged from 125 to 190 beats per minute (bpm), with a median of 150 bpm; in the adrenaline group, they present a maximum heart rate of 165 bpm, with their median close to 140 bpm (p=0.000); Systolic blood pressure in the Dopamine group ranges between 30 and 60 mmHg, with extreme values for the lower portion of up to about 25mmHg; In the Adrenaline group, the distribution ranges between 30mmHg and 60mmHg, with extreme cases in both directions of the distribution, having a value of close to 25mmHg and an extreme value close to 70mmHg. The medians of both distributions have an approximate difference of 5mmHg, being 50mmHg in the
Discussion
Our results contrast with the double-blind prospective randomized controlled study carried out in Brazil (Ventura et al.) That compared the use of adrenaline vs dopamine, observing better results and longer survival with the use of adrenaline, compared to dopamine, which presented greater effects, adverse events and increased mortality; similarly, another double- blind randomized study comparing the use of dopamine and epinephrine in paediatric patients with septic shock performed (Ramaswamy et al.) evaluated the vasopressor effect and found adverse effects with dopamine compared to epinephrine; in the same way as another study (Baske et al) carried out in neonates, where hemodynamic improvement was observed with the use o adrenaline1,9,10.In Bolivia (Viruez et al), it was found that there was no difference in mortality between the use of norepinephrine and dopamine after 7 days of treatment, but higher mortality with the use of dopamine after 24 hours of treatment.11
Our study is the first in Bolivia in paediatric patients comparing use of epinephrine with dopamine, showing few adverse effects, but same mortality rates, however, the size of the sample limits the scope of our conclusions to the experience of a single-centre study with only a hospital follow-up period. 11
Therefore, we conclude that both dopamine and epinephrine have similar effects in terms of hemodynamic response, with the mention that dopamine has a greater impact increasing heart rate (p=0.000); In addition, both drugs had a similar response to treatment, recovery time and survival, reflecting what eventually happens in other hospitals in limited-resources settings, and can be used in second level hospitals to stabilization of paediatric septic shock.
Interest conflict: Nothing to declare.
Acknowledge: Dr. Raul Copana, Dr. Alejandro Martinez for mentoring this study.
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