Prevalence of Pain in Mechanically Ventilated Patients in Intensive Care Units

PARTICIPANTS AND METHODS

ETHICAL ASPECTS

This project was submitted to the Ethics and Research Committee (CEP) of UNISUAM, via Platform Brazil, by the project coordinating center and will have the consent of all participating institutions, as per and predicted in the standards from the Resolution 466/12, of Advice National of Health (CNS) (Brazil, 2012) and in Law 14,874/2024, which establishes the National System of Ethics in Research with Human Beings (Brazil, 2024) and approved under number: 83431424.8.1001.5235 . Like this, the investigators ensure what principles ethical will be followed to the far away from the search, with one commitment explicit of respect the autonomy and these values of participants, while ensuring the confidentiality of data. All data will be reported later following the recommendations of STROBE ( STRengthening the Reporting of Observational studies in Epidemiology).

LOCATION OF REALIZATION OF STUDY

The study will be a multicenter study involving public and private hospitals, with the coordinating center of the study being the Augusto Motta University Center

SAMPLE

The sample size for qualitative variable and quantity variables are different and were based on previously study . Thus, as our primary outcome will be the assessment of the prevalence of pain in mechanically ventilated patients and this classification will be dichotomous, the investigators will use the sample calculation for qualitative variables.

For qualitative variable

To find out the proportion of patients who experience considerable pain in the ICU (BPS > or = 5) in a population, the investigators use the formula below since this proportion is qualitative.

Sample size = [ Z 1-α/2 2 xpx(1-p)]/d 2 ]

Being:

Z 1-α/2 = It is a standard normal variable (assuming 5% type 1 error (p<0.05) it is 1.96 and with 1% type 1 error (P<0.01) it would be 2.58). Since in most studies P values are considered significant below 0.05, therefore 1.96 was used in the formula.

p = Expected proportion in the population based on previous studies d = Absolute error or precision - sênior investigators decided on an absolute error of 5%

In this case, to estimate the proportion of participants with considerable pain experience (BPS ≥ 5) in volunteers admitted to intensive care units under mechanical ventilation and in accordance with previous studies that establish an estimate of a BPS ≥ 5 at 40%, the sample size was calculated with a precision error of 5% and a type 1 error percentage of 5%.

Sample size = [1.96 2 x 0.4 x(1-0.4)]/0.05 2

Therefore, for this cohort, multicenter study, 370 participants will be evaluated .

LOCATION OF RECRUITMENT

All participants will be recruited from the ICUs of participating hospitals between june and december to 2025.

PROCEDURES

STANDARDIZATION OF COLLECTION PROCEDURES

Researchers from the study's Coordinating Center will conduct online training with the heads of each participating center and will provide an instructional video on the collection procedures. All data will be entered into a database with input masking and coded using Research Electronic Data Capture (REDCap).

CLINICAL DATA

Data on age, sex, body weight, height, surgery, SAPS 3 score ( Simplified Acute Physiology Score 3) and Sequential Organ Failure Assessment (SOFA) will be collected at the time of ICU admission. Information on time to successful weaning from mechanical ventilation, time to successful discharge from the ICU and 28-day hospital mortality will also be collected.

PROCEDURES

All participants will be evaluated at two moments: second day after mechanical ventilation and on the first day of sedation suspension, with superficialization confirmed by a RASS ≤ -2 (-2 to +2). The evaluations will always occur at the same time, in the morning, after the routine tracheal aspiration procedure (which is known to be one of the main causes of pain in mechanically ventilated patients). All evaluation procedures will occur during the first physiotherapy appointment during the daytime period on the respective days.

Pain will be assessed by the Behavioral Pain Scale and the Critical Care Pain Observation Tool, which are tools validated in Brazil and are widely used to assess critically ill, uncooperative patients.

At this time, the asynchrony index (AI, %) will also be evaluated, calculated as the ratio between the number of asynchronous cycles/total ventilatory cycles studied X 100.

These assessments will be carried out at least 1 hour after bathing or nursing care procedures to wash out any painful experiences that may arise.

The entire pharmacological strategy will be expressed in dose/weight/time. Patients will be divided into two groups: a "pain" group in which BPS ≥ 5 and a "no pain" group in which BPS < 5. The criterion for establishing the cutoff point at BPS values BPS ≥ 5 was determined based on previous studies that defined it as a "pain event", or as an "inadequate state" of pain.

ANALYSIS OF DATA

The data will be collected by the coordinators or routines of the ICUs of the participating centers, using an input mask, being coded and later evaluated by an independent statistician, who did not participate or will not participate in any stage of the project execution.

FLAT OF ANALYSIS STATISTIC

Results will be expressed as numbers (%) for categorical variables and medians (interquartile range) for continuous variables. The primary outcome measure for this project will be pain intensity before and after a painful stimulation procedure using the BPS on a scale of 3 to 12 and the CPOT on a scale of 0 to 8.

Univariate logistic regression analysis will be used to identify parameters associated with pain events in the event group. Normality of data will be checked using the Kolmogorov-Smirnov test, while homogeneity of variance will be checked by the F test. Student's t-test or Welch's test, or the Wilcoxon test will be used for continuous data, as appropriate. Chi-square or Fisher's exact test will be used for categorical variables. After that, a multivariate logistic regression analysis will be used to determine factors independently associated with pain in the groups categorized as "pain" (BPS ≥ 5) or "no pain" (BPS < 5). Variables will be entered into a model when they were associated with pain status.

This will be based on a univariate logistic regression analysis significance threshold of p < 0.1, and when there is no mutual correlation, based on a Spearman correlation coefficient greater than 0.7 or less than -0.7. The final model will be constructed using backward elimination of non-significant variables. Odds ratios and 95% confidence intervals (95% CI) will be calculated based on the likelihood ratio statistic. Comparative analyses of the three components of the BPS and CPOT will be performed using the Friedman test followed by the Dunn test and multiple comparison test. Univariate analysis of clinical outcomes will be performed for time to successful weaning from mechanical ventilation, time to ICU discharge, as well as 30-day in-hospital mortality rate using the log-rank test. In addition to these univariate analyses, clinical outcomes will be assessed using multivariate analyses.

Logistic regression analysis, correcting for risk factors, will use variables that present at least a trend towards significance (p < 0.1) in the univariate analysis. The parameters will be checked for linearity and non-linear parameters will be entered into the model as nominal variables. Odds ratios as well as 95% CI will be calculated for the outcomes. All values that result in two-sided statistical tests with a p value ≤ 0.05 will be considered significant. R statistics (R, version 2.15.2) were used to analyze the data. The analyses will be computed using R Software (version 2.15.2).

AVAILABILITY OF ACCESS TO THE DATA

All data of present study will be available through of one universal data repository, in addition to the virtual library and database of UNISUAM and each center participating in the study

RESULTS EXPECTED

This research project will provide a current data set on pain in mechanically ventilated patients, using two validated tools for this screening and will correlate the presence of pain with clinical factors, sedation and analgesia regimen employed, with the presence of patient-ventilator asynchrony and thus with hard outcomes related to length of stay in the ICU, time to weaning and 28-day mortality in the ICU.