Introduction
A major challenge for managers in the hospital setting is to ensure patient safety, and one should consider the investigation of adverse events (AE)in the analysis of indicators of quality of care. In the intensive care unit (ICU), a department for the care of critically ill patients1,there is a higher probability of occurrence of adverse events due to clinical instability of patients and the high number of interventions and devices to which they are subjected during treatment2.
The occurrence of AE is to be discussed as one of the aspects that negatively impact patient safety, especially since 1999, with the release of the report To Err is Human by theInstitute of Medicine(IOM). This report was based on the evaluation of the incidence of AE that occurred in three hospitals in the United States of America (USA) that found that approximately 100,000 people die in USA hospitals everyyear, victims of AE, with a consequent significant increase in healthcare costs3.
Five years after the publication of this report, the World Health Organization (WHO) created the World Alliance for Patient Safety, which highlighted the main aspects of patient safety and the factors that can influence it, such as AE. According to the WHO's definition, incidents are events or circumstances which may result or have resulted in unnecessary harmto the patient, whereas AE are incidents arising from unintentional mistakes that cause measurable lesions4.
In 2013, the National Program of Patient Safety (PNSP, in Portuguese) was established in Brazil by the Ministry of Health, elaborating and implementing a set of basic protocols in health institutions5.Ordinance No. 1,377 adopted on July 9, 2013, sets protocols for safe surgery, hand hygiene practices, and pressure ulcer avoidance6. After a few months, a new ordinance was published (Ordinance No. 2,095, September 24, 2013) setting new protocols: prevention of falls, safety in prescribing and in the use and administration of medications, as well as in patient identification7.These protocols act as guides, setting standards that must be used in hospitals and support best practices with a focus on patient safety7.
In the intensive care environment, the quality of nursing care and patient safety depends not only on the qualification of professionals, but also on the appropriate quota of human resources available.However, health services still face extreme difficulty in matching the number of professionals with the demand, generally due to financial issues. The numerical and qualitative mismatch between human resources and the carerequired by patients in intensive care can lead to work overload and failures in the process of care8.
Nursing workload can be defined as "work process elements that interact dynamically with each other and with the body of the worker, generating a process of adaptation which leads to wear"9. Acknowledging this load in the workplace is essential, since it is subject to control and reduction of undesirable effects10. However, ignoring the importance of its measurement may cause a negative impact on the quality and safety of care to patients, due to the greater likelihood of AE.
Therefore, the assessment of nursing workload is a subject of great relevance, insofar as an oversized team implies higher costs. On the other hand, it is known that a reduced team can cause a drop in effectiveness and/or quality of care, extending the length of hospital stay and generating greater costsof treatment, in addition to exposing patients, staff, and the institution itself to the risk of not having safe care11-12.
Studies show thatan increase in hours of nursing care provided to patients is associated with adecrease in the occurrence of AE, such as: urinary tract infection;pressure ulcers; hospital-acquired pneumonia; wound infections; complications in central venous access; shock; thrombosis; medication errors; and postoperative complications13-14. Another publication shows that the nursingworkload is a risk factor for death in the ICU15.However, no systematic reviews were identified from the literature showing apossible relationship between workload and AE in the scope of nursing.
In this context, the authorsinquire: Is there an influence of nursing workload on the incidence of AE in patients admitted to the ICU? The answer to this question may provide contributions to intensive care managers and nurses in the use of nursing workload measurement tools in order to justifythe appropriate staff size in intensive care, ensuring care safety. The objective of the present review was to find evidence of the influence of nursing workload on the occurrence of AE (pressure ulcers, infection, falls, or medication errors) in adult patients admitted to the ICU.
Method
This is a systematic literature review, which consists of a rigorous synthesis of relevant results on a given theme, in which the main goal is to indicate the best available evidence on the effect of a particular therapy or intervention, so that professionals are aware of the best practices described in the literature16.
Data were collected through electronic search from October to November 2015 in the following databases: the Medical Literature Analysis and Retrieval System Online (MEDLINE);the Cumulative Index to Nursing and Allied Health Literature (CINAHL);the Latin American and Caribbean Center on Health Sciences Information (LILACS);the database of nursing (BDENF); and the Cochrane library. The portal Scientific Electronic Library Online (SciELO) was also analyzed. In addition, grey literature was analyzed through Google Scholar and a manual search was undertaken from the references cited in the articles selected.
Adverse events analyzed in this review include pressure ulcers, infections, falls, and medication errors. These events were selected from the proposal of the basic protocols previously described6-7.
The PICO strategy (which is an acronym for Patient, Intervention, Comparison, and Outcomes)17, was used for the elaboration of the main question in this research. In order to find relevant studies that would respond to the studyquestion,indexed and non-indexed descriptors (keywords) were used inPortuguese, English, and Spanish. The descriptors were obtained from the Medical Subject Headings (MESH), the Health Sciences Descriptors (DeCS, in Portuguese), and CINAHL titles, as shown in the following chart.

Chart 1 Elements of the PICO strategy, descriptors (MESH, DeCS and CINAHL titles) and keywords used-São Paulo, SP, Brazil, 2016.
The element C from the PICO strategy has not been addressed in this research, as this is not intended to compare interventions. The keywords (MESH and DeCS) and the titles from CINAHL were combined with the Boolean operators "OR" and "AND." The following criteria were used to guide the inclusion of articles in the review: studies published in full in national and international journals in English, Portuguese, or Spanish and whichmake use of instruments for measuring the workload of nursing in adult patients in the ICU. No filters were applied to the period of publication of the articles. Research on pediatric populations, as well as journaleditorials, letters to the editor, comments, theses, and dissertations were excluded from the sample.
Considering the singularitiesand distinctive features of the databases, the search was carried out using different strategies, as described in Chart 2.

Chart 2 Search strategies used in the databases MEDLINE, CINAHL, LILACS, SciELO, BDENF and Cochrane - São Paulo, SP, Brazil, 2016.
Studies retrieved from the search strategy had their title and abstract evaluated, so as to identify those pertinent to the subject at hand. In studies where the given data were not enough to determine whether or not they should be included, the study in question was considered for the shortlist, so as to avoid mistaken exclusions.
Preselected studies were recovered in their entirety and analyzed independently by two researchers. In the case of disagreement between them, a third researcher conducted ananalysis of the research, so as to ensure the prevailing opinion of the majority.
To extract the data from the articles, we used an instrument containing the following information: title; author; journal; year and country of publication; research objectives; methodological design; measuring instrument of nursing workload used; type of adverse event analyzed; main results; and conclusions.
To assess the quality of the studies included in the review, two researchers independently applied the instrumentStrengthening the Reporting of Observational Studies in Epidemiology (STROBE), which consists of a checklist with 22 items about recommendations on what should be included in a more accurate and complete description of observational studies18. It should be noted that this analysis was carried out not for the purpose of exclusion, but for description of sample studies.
Due to the heterogeneity of the methodology of the studies included in the review, it was not possible to perform meta-analysis.
Results
From the search strategy employed, 596 potential studieswere recovered, with the largest number of studies found in the MEDLINE database (n = 345), followed by CINAHL (n = 226), LILACS (n = 14), BDENF (n = 6), SciELO (n = 3), and Cochrane (n = 2).
Figure 1 presents the process of study selection. Only eight of 37 studies preselected for reading in full met the eligibility criteria of this review and comprised the final sample.

Chart 3 Distribution of studies according totitle, objective, design, country and year of publication-São Paulo, SP, Brazil, 2016.
None of the studies in Chart 3 showed agreementwith all items of the STROBE. However, all of the research in this review hasincluded at least 50% of the items. Of the eight studies included in the review, three (37.5%) were carried out in Brazil23-25and two (25.0%) in Turkey21,26. Chile19, Slovenia20,and Belgium22contributed with one study each (12.5%).
The searches were performed between 2000 and 2013 and publishedbetween 2005 and 2015in English20,22,24, Spanish19, Portuguese25or in all three languages: English, Spanish and Portuguese21,26. A total of six studies (75.0%) were published in international journals19-24and two (25.0%) in national journals25-26. There has been a higher percentage of prospective studies (75.0%)19-21,23-25, especially of the cohort type19-20,23-25.Retrospective investigations were performed less frequently (25.0%)22,26.
Chart 4 shows that the sample analyzed in the searchesranged from 79 to 970 patients in the ICU19-26.Of the studies that described the characteristics of patients in the results21-24,26, it was possible to identify the prevalence of women21-22,24,26ranging from 50.9 to 65.6 years of age21-24,26. Regarding the instrument of workload applied, three studies (37.5%) used theNursing Activities Score (NAS)23-25,three (37.5%) the Therapeutic Intervention Scoring System (TISS), either the original20or the version with 28 items19,22, and two (25.0%), the OmegaScoring System(Omega) and the Project de Recherché en Nursing(PRN)21,26.
Regarding the types of AE, healthcare-associated infections (HAI) were examined in five studies(62.5%)19-21,23,26.Occurrence of pressure ulcer24-25 was a less frequently investigated AE (25.0%), as was medication error (25.0%)22,25. Adverse events involving accidental loss of central venous catheter, obstruction or loss of the nasogastric tube, loss or damage tothe endotracheal tube cuff, loss of bloodline, and falls were also considered as AE in the Chilean study and were referred to as sentinel incidents by the authors19.
Most of the eight studies included in the review found an influence of nursing workload on the occurrence of different AE: infection20-21,23,26,pressure ulcer25, and drug use22,25. A Brazilian study that analyzed the occurrence of pressure ulcers in intensive care concluded that nursing workload was a protective factor for the outcome24. A study showed that the TISS-28 exerted influence only on mortality, that is, there was no relationship between nursing workload and the occurrence of sentinel incidents, including falls or infections, in the ICU19.

SI: No information; TISS: Therapeutic Intervention Scoring System; Omega: Omega Scoring System; PRN: Project de Recherché en Nursing; SOFA: SequentialOrgan Failure Assessment;NAS: Nursing Activities Score; OR: Odds ratio; CI: Confidence interval.
Chart 4 Characteristics of studies included in the review according to the sample and patients' characteristics, analyzed AE, applied instrument of nursing workload, results and influence of nursing workload on occurrence of AE -São Paulo, SP, Brazil, 2016.
Discussion
From the full analysis of selected studies in this review19-26, it was found that nursing workload influences the occurrence of AE in patients admitted to the ICU.
Regarding the instruments of measurement of nursing workload, there was a greater amount of studies that applied the NAS23-25or the TISS19-20,22in patients analyzed. The NAS, developed by Miranda et al. in 2003, is an instrument that analyzes 23 items (nursing activities), with scores ranging from a minimum weight of 1.2 to a maximum of 32.0. The total score is obtained by summing the points, and directly expresses the percentage of time spent by a professional of the nursing staff in the care of a patient in critical condition over 24 hours27. The NAS was translated and validated in Brazil byQueijo and Padilha in 200912.
Amongst the studies that used the NAS, all were carried out in Brazil and displayed meanvalues of nursing workload between 61.97% and 81.2%23-25. These values are close to those of other studies that applied the NAS in Brazilian ICU28-30. However, when analyzing the meanNAS scores in relation to international studies, discrepant results are found: approximately 41% NAS in Spanish studies31-33, but more than 95% in Norwegian research33. Among the contributing factors to the different findings betweenthe national and international literature, one must consider the clinical characteristics of the patients, the specific features of the ICU, and the heterogeneity in the interpretation and application of the instrument.
Considering the minimum (61.97%) and maximum (81.2%) meansof NAS found in this review and that 1 NAS point is equivalent to 14.4 minutes27of nursing care, it can be concluded that the patients analyzed in these studies23-25required minimal careof approximately 14.9 hours and maximum care of 19.5 hours in a period of 24 hours in intensive care. Comparing these values with those recommended by the resolution of the Federal Council of Nursing (Cofen-293/2004)34which considers, for sizing purposes, 17.9 hours of careprovided by the nursing team to a critical patient, the minimum meanpercentage of NAS is within established parameters. However, for the maximum meanpercentage, there is a possiblework overload among nursing staff.
Instruments TISS or TISS-28, used in three studies19-20,22,were precursors of the NAS. The TISS, created by Cullen et al. in 1974, was the pioneer measurement system of nursing workload. The TISS presupposed that the more serious the patient condition, the greater the number of interventions carried out, regardless of the diagnosis presented35. This instrument underwent various modifications and simplifications, and the latest version, the TISS-28, analyzes 28 items, divided into seven groups: basic activities, ventilatory support, cardiovascular support, renal support, neurologic support, and metabolicsupport, in addition to specific interventions. The variation of TISS-28 score is 1 to 78 points, each point of the score being equivalent to 10.6 minutes of carefrom a nurse to an ICU patient36.
The practical application of TISS-28 showed weaknesses, since activities related to indirect care to patients, such as administrative and managerial tasks, as well as family support, were not addressed. In order to fill this gap, the same group of researchers proposed the creation of the NAS in 200327, as described earlier. It should be noted that both the TISS-28 and the NAS instruments were created from multi-center studies, with the participation of ICU staff from different countries and continents.
Omega and PRN were applied in two studies carried out in Turkey by the same group of researchers with the purpose of analyzing the relationship between colonization or infection by MRB and nursing workload21,26. The first scale was developed in Canada in 198137and, the second in France in 198638. The use of instruments formeasuring nursing workload developed in a single country can result in restrictions in application and generalization of results, because they reflect the characteristics of the population to whomthese instruments were created.
Regarding the design of the studies, the majority was of the prospective type19-21,23-25. This type of method is more time consuming and costly, but has the advantage of presenting less bias, because variables such as lack of information can be controlled,allowing for more reliable results39. Prospectively collected data may explain the reduced time span of the studies (3 to 8 months) and, consequently, the small size of samples (138 to 3800)19-21,23-25.Only one prospective study, conducted in an ICU with 11 beds in Slovenia20, examined patients admitted to the intensive care unit during three years, allowing the investigation of a larger number of patients (n = 970). One must take into account that small samples, often from a single ICU, may restrict the application of the results in other populations, because they represent the specific reality of the units evaluated.
Among the AE analyzed, HAIwere the most frequently considered by researchers19-21,23-26. Such an interest may be justified by the fact that HAIare factors associated with extending length of hospital stay, generating high levels of health complications and increasing care costs, as well as favoringthe selection and spread of multiresistant organisms40, making this event one of the focuses of interest of the PNSP. In this respect, the practice of hand hygiene, created with the aim of preventing and controlling HAI, defined the five major moments in which the hands must be sanitized as well as the technique itself41.
Of the five studies that analyzed these AE, most (80.0%) identified that high workload is a risk factor for occurrence of HAIin intensive care20-21,23,26. Brazilian researchers stressed that HAIhad an influence onthe overload of nursing work, characterized by a NAS score equal to or greater than 51%, because, in the units of study, each nursing professional provides care to two patients per shift23. In this respect, when analyzing the workload of nursing care required by patients, one must consider the number of professionals available to answer it, because this variable directly impacts the quality of care and occurrence of AE42-43. Only one investigation failed to identify the relationship between nursing workload and HAI19. The authors explain this finding, emphasizing that patients in more severe conditions require more care and are more closely monitoring in the ICU and therefore have greater protection against AE19.
The overload of nursing work also influenced the occurrence of AE related to medications22,25.Research conducted in the U.S. revealed that in the country's hospitals each patient admitted is susceptible to one medication error per day44. In a Brazilian study performed in an ICU, of the 550 AE identified, 283 were related to medication errors19-21,23-25. It must be considered that this type of AE in the ICU can be fatal due to the severity of the clinical condition of the patient and the complexity of the drug therapy46.
The high incidence of this event became one of the focuses of the Ministry of Health which, together with the National Health Surveillance Agency (ANVISA, in Portuguese), launched a safety protocol on the prescription, use, and administration of medicines, indicating safe practices such as: confirming the patient's ID on the prescription; the use of the full name and date of birth;the signature and stamp of the prescriber; identification of allergies; dosage;titration; infusion speed; and route of administration of the drugs prescribed. In addition, the protocol recommends safe practices in relation to the storage and disposalof medicines47.
Although studies show that falls in the hospital environment are related to a lack of quality of care and have unforeseen consequences to the patient such as abrasions, contusions, lacerations, and fractures48, studies ofthis event in the ICU are limited. In this review, only one investigation addressed the topic19and did not identify the influence of nursing workload on the occurrence of this AE. The scarcity of studies that address this AE in the ICU can be related to a low incidence of falls with injury to the patient in this type of unit, becausecontinuous monitoring is one of the features of intensive care.
Despite investment in devices for the prevention and treatment of pressure ulcers in intensive care, there is still a high incidence of this event in patients hospitalized in critical care units49-51. In this respect, two Brazilian investigations24-25analyzed the possible influence of nursing workload on this AE and found contradictory results.
Research conducted in ICU of two public hospitals showed that there were 2,317 AEin 399 admissions occurred between May and August 2009, and dermatitis, diaper rash and pressure ulcers were the most frequent (60.45%). In this study, patients with an NAS equal to or higher than 51.0% were about three times more likely to report at least one AE in the ICU than those with an NAS lower than 51%. The authors have reinforced the importance of communication among personnel managers and nursing coordinators regarding detailed analysis and dynamics of the sectors with a focus on people management and sizingof the team25. Other research carried out in an ICU in São Paulo, Brazil, showed that the NAS had a significant negative correlation with the Braden scale, which assesses the risk of the patient developing a pressure ulcer52. However, the NAS was a protective factorfor the occurrence of pressure ulcers in the sample. According to the authors, results indicate that the care provided is adequate in preventing injury and suggested that other risk factors, such as severity, length of stay in the ICU, and gender should be considered, as these variables contribute to the development of this type of injury24.
In most studies, results of this systematic review showed that nursing workload, analyzed by different instruments, had an impact on the occurrence of AE in patients during hospitalization in ICU. According to the literature, AE generate an impact on the quality of care, with increased rates of mortality, longer hospital stays and, consequently, higher welfare costs53. In this regard, the importance of analyzing the workload of nursing required by patients is necessary in order to establish a proper relationship between the number of nursing professionals and patients, focusing on the prevention of AE and ensuring patient safety.
Conclusion
The influence of nursing workload required by patients in intensive care was identified as a risk factor for the occurrence of the AE infection, pressure ulcers, and/or medication errors in six of the eight studies examined. In one investigation, workload was identified as a protective factor for pressure ulcer development.
Intensive carenurses must monitor the daily nursing workload required by patients, using the tools available in the literature, such as validated scales in the country, to measure this variable, and be attentive to those occurring in the unit due to work overload, because this can exert a negative influence on patient safety.
The results of this review reinforce the need to conduct multicenter studies, with larger samples and longer follow-up to strengthen the evidence of the relationship between nursing workload and the occurrence of different AE in intensive care.