Risk factors for death in patients with non-infectious adverse events

ABSTRACT Objetive: to identify risk factors for death in patients who have suffered non-infectious adverse events. Method: a retrospective cohort study with patients who had non-infectious Adverse Events (AE) in an Intensive Care Unit. The Kaplan Meier method was used to estimate the conditional probability of death (log-rank test 95%) and the risk factors associated with death through the Cox regression. Results: patients over 50 years old presented a risk 1.57 times higher for death; individuals affected by infection/sepsis presented almost 3 times the risk. Patients with a Simplified Acute Physiology Score III (SAPS3) greater than 60 points had four times higher risk for death, while those with a Charlson scale greater than 1 point had approximately two times higher risk. The variable number of adverse events was shown as a protection factor reducing the risk of death by up to 78%. Conclusion: patients who had suffered an adverse event and who were more than 50 years of age, with infection/sepsis, greater severity, i.e., SAPS 3>30 and Charlson>1, presented higher risk of death. However, the greater number of AEs did not contributed to the increased risk of death.


Introduction
Adverse Event (AE) is understood as the unintentional injury caused to the patient, not related to the underlying morbidity, as a result of the interventions of the health team and that can generate prolongation of the hospitalization time, suffering, physical and emotional discomfort, incapacity and death (1) .
Patients hospitalized in Intensive Care Units (ICUs) are particularly vulnerable and susceptible to the occurrence of these injuries due to the severity of their clinical condition, the instability of their condition, the need for constant and numerous emergency interventions performed by the multidisciplinary team involved in the assistance, as well as the large number of diagnostic procedures and the use of specific and complex drugs (2)(3)(4)(5) .

Studies on adverse events in patients admitted
to ICUs have become more prominent in publications since 1995. It is worth noting the study performed in an ICU of a hospital in Jerusalem, which verified the occurrence of 1.7 errors for each patient per day, which occurred in an average of 178 activities performed by practitioners involved in the care, and 29% of these errors were classified as probable cause of serious clinical complications or even death (6) .
In a study carried out in Belgium in 2012, it was verified that the percentage of death ranged from 0% to 58% and the length of stay in the ICU ranged from 1.5 to 10.4 days (7) . In the US, in 2013, between 210,000 and 440,000 deaths were associated with adverse events and almost half of these could have been avoided (8) , and in 2016 the Leapfrog Group estimated 206,201 avoidable deaths, with 33,439 lives that could be saved each year if all hospitals had a good performance regarding the safety of their patients (9) . Also in 2016, Makary and Daniel's report to Johns Hopkins University estimated that the number of avoidable deaths was estimated at more than 250,000 (10) .
In Latin America, according to data collected from 58 hospitals, the prevalence of adverse events was 10.5% (95% CI 9.91 to 11.04), with 28% resulting in disability and 6% in the death of the patient. It is worth mentioning that 60% of AE were considered avoidable (11) .
In Brazil, in 2009, the incidence of AE found was 7.6%, and in 2011, 2.9% of events were associated with death of patients (12)(13) .
In Rio de Janeiro, the main types of non-infectious adverse events were due to delayed or failed diagnosis and/or treatment and development of pressure ulcers (14) . At the same city, a prospective cohort study in an intensive care unit found that the incidence rate of adverse events was 9.3 per 100 patient/day and the occurrence of adverse event resulted in a 19-day increase in length of stay and doubled the chance of the individual evolving to death (OR=2.047, 95% CI: 1.172-3.570) (15) .  The concept of non-infectious adverse event, used in the present research, was "the set of errors actually occurred (generating or not non-infectious damage to the patient) and all non-infectious damage related to the care process" (17) .
In the analysis of the adverse events occurred due to medication the main drugs and the severity of the event were detailed; and in the event of pressure ulcer, the main place of occurrence was highlighted. The number of events occurred in the same patient was also evaluated, as well as the types of events.  (12) .
To evaluate the Simplified Acute Physiology Score III (SAPS3), a severity score, we analyzed the demographic variables, the comorbidities, some specific diagnoses, the use of invasive support, as well as physiological and laboratorial variables present in ICU admission (18) . Through SAPS3, a score is obtained from which the probability of hospital death is estimated. In the interpretation of the score, we consider that the highest number of points, the higher the severity of the patient (12) . Also to express the severity profile due to comorbidities, the Charlson score was used, in which scores were assigned from one to six for the 17 clinical conditions (12) .

Results
Among the 792 patients admitted to the ICU in the period evaluated, 36.2% had some type of noninfectious AE, the majority being male and older than 50 years. The variables length of stay in the ICU, type and reason for hospitalization, use of mechanical ventilation and vasopressor drugs, score of less than eight points in the Glasgow coma scale and higher mortality risk measured by SAPS3 showed statistically significant differences between individuals who had suffered noninfectious AEs when compared to those who had not (Table 1).  Of the total of patients who had suffered noninfectious AEs, 43.6% had suffered more than one event.
Among the AEs, the pressure ulcers represented almost half of the events, being located mainly in the sacral and calcaneal regions, followed by the use of probes, drains and catheters, and those related to medication and blood transfusion (

Discussion
The present study points out that the risk of death in patients with non-infectious AEs is not due to the number of events that the patient suffered, but rather to the severity of the patient and to the presence of comorbidities. It was also observed that, when comparing individuals with and without non-infectious AEs, the length of stay, the type and reason for hospitalization, and the variables related to patient severity (SAPS3, Glasgow, use of mechanical ventilation and vasopressor) presented statistically significant differences. This result is consistent with both the international and national literature and the explanation is linked to a prolonged stay, presence of comorbidities and greater severity of the patients (3,5) .
This study identified 36.2% of cases of AE in the analyzed patients, a figure higher than that found in countries such as Canada, the United States and France, where 19%, 20.2% and 31% of patients had suffered at least one AE, respectively (19)(20) . We must take into account that the number of nursing It is worth mentioning that in the studied ICU the increase in the number of AEs represented a protection factor probably related to the greater non-infectious post-AE care adopted by the team, as well as the greater attention given to these patients because they are patients with greater severity.
In 2014, in Japan, a study to verify the influence of AEs occurred due to use of drugs found that 15% were drug-related, with an incidence of 30.6 per 1000 patients per day, of which 70% were 65 years or more and the mean length of saty of individuals who had suffered at least one drug-related AE was 13 days (25) .
In Brazil, a study carried out in the state of São Paulo, in 2014, demonstrated that the most common AEs, which are under the responsibility of the nursing staff, were dermatitis, rash and pressure ulcer, corresponding to 60.4%, thus evidencing, as in our study, that skin injuries were the most found AEs (5) .
In Piauí, 29% of the patients presented pressure ulcers, 58.3% of which were located in the sacral region (26) . These high figures, especially with regard to the location in the sacral region, suggest that measures for pressure ulcer prevention have not been adequately observed by the health team.
Thus, it is necessary to adopt measures to prevent pressure ulcers. In addition to providing an adequate nutritional contribution, body hygiene and use of moisturizers and humectants for skin, it is of great importance to protect bony protrusions, identify risk factors targeting treatment, make record of skin changes, make use of risk assessment scale, change of decubitus every two hours and, among others, monitor and register interventions and their respective results (27) .
In 2015, a study in Jerusalem found that patients with pressure ulcer in the sacral region had lower survival rates than those without pressure ulcer (70 days versus 401 days) (30) .
A study conducted in Canada in 2008 showed that the risk of death was 1.4 times higher; in France, the risk was about twice as high in patients who presented high SAPS3, a figure below that found in our study (21) . In the present study, advanced age and the presence of infection also increased the risk that the individual affected by an AE evolved to death by 1.57 and 2.62 times, respectively. In the US, sepsis had a significant impact on the mortality of individuals over the age of 60, increasing by almost two times the risk of death, as well as old age itself at 1.04 times and Charlson at 1.14 times (31) .  (32) .
Considering the retrospective design of this study, we are not allowed to evaluate other information necessary to better explain the work and, despite the large number of adverse events identified, it is possible that this number is even greater when considering underreporting.
However, as strengths, it is due to its outline that this study contributes in a positive way to allow inferences of its results, in addition to its unprecedented nature, since any work on the subject in the Amazon region is unknown, which favors the knowledge of the reality on this subject in Brazil.

Conclusion
Patients who had suffered an adverse event and who were more than 50 years of age, with infection/sepsis, greater severity, i.e. SAPS 3 > 30 and Charlson > 1, presented a higher risk of death; however, the greater number of AEs did not contribute to increase the risk of death among the evaluated patients.
The notification of adverse events in the intensive care unit is an important way to control the quality of care, because the identification of failures allows investing in preventive measures and, thus, avoiding damages to the patients. In order to reduce the occurrence of noninfectious AEs, it is necessary to invest in qualification and updating of the professionals involved in the assistance, enough human resources to meet the demand, physical structure and adequate technology.