Continuous Positive Airway Pressure During General Anesthesia Induction For Elective Pediatric Surgery: Randomized Clinical Trial
Phase: NA
Conditions: Continuous Positive Airway Pressure, Hypoxia, General Anesthesia
Sponsor: Instituto Materno Infantil Prof. Fernando Figueira

Continuous Positive Airway Pressure During General Anesthesia Induction For 
Elective Pediatric Surgery: Randomized Clinical Trial
NCT03432390
02/28/2018

General anesthesia can be defined as a transient stage of drug-induced unconsciousness through its 
actions on molecular receptors1,2. Little is known about its mechanisms, but this state is supposed 
to be an adaptive phenomenon as sleep1. It is a reversible condition that has specific behavioral and 
physiological patterns (unconsciousness, amnesia, analgesia, and akinesia). It consists of three 
phases: induction, maintenance and emergency or awakening2. 
Anesthetic induction is the period in which the administration of hypnotic drugs (venous, 
inhalational or a combination of both) begins 2,3. At this stage, an irregular breathing pattern 
progresses to apnea. Ventilatory assistance is then initiated by the anesthesiologist, usually through 
a face mask and reservoir bag2,4. 
Inhalation induction is a safe, feasible and well-accepted patient technique widely used in children 
or, exceptionally, in adults with difficult venous access. However, it is not a risk free method. 
Complications such as cough, laryngospasm, salivation, induction failure and voluntary apnea may 
increase the morbidity of the anesthetic procedure3,5. 
The effects of general anesthesia on the respiratory system are well established. Among them, there 
is a greater predisposition to airway obstruction and collapse. Its mechanisms are not clearly known, 
although some associations have been documented (ventilatory muscle relaxation, anesthesia dose-
effect relationship and airway patency impairment) 6,7. Loss of respiratory muscle tone due to 
anesthetic induction is related to lower airway collapse, reducing functional residual capacity (CRF) 
7. 
Another additive explanation for airway collapse is the pharmacological impact of drugs used for 
sedation and hypnosis in processes that control both the efferent motor pathways of the pharyngeal 
muscles and the mechanoreceptor afference6. 
Inhalational anesthetics exacerbate dynamic airway collapse, especially in the soft palate, and are 
directly associated with the administered dose of the drug. Sevoflurane acts by reducing the 
inspiratory phasic activity of the genioglossus muscle without compromising its tonic activity. Even 

at sedative levels, sevoflurane modifies airway dimensions, reducing its patency especially on 
inspiration6. 
As with inhaled drugs, venous anesthetics also act on the respiratory system. Propofol reduces the 
cross-sectional area of the upper airway, a reduction that has been shown to be maximum at the base 
of the tongue when sedative doses are used. Induction with this agent reduces the 
electromyographic activity of the genioglossus muscle6. 
During the apnea period following general anesthesia induction, oxygen stores (O2) are being 
consumed which may result in hypoxemia8. Oxyhemoglobin desaturation is faster in patients with 
reduced O2 transport capacity, ie, those with reduced CRF, partial oxygen pressure (PaO2), arterial 
oxygen content and cardiac output, or increased oxygen uptake (VO2). ) 9. 
General anesthesia appears as a major risk factor for mortality in pediatric surgical patients, and 
problems with airway management in patients with comorbidities appear to add life-threatening risk 
to this population10. Pediatric patients, in turn, have more frequent episodes of desaturation during 
induction (4-10%) 5,8,11,12. Children undergoing a greater number of tracheal intubation attempts, 
considered to have a difficult airway, are at greater risk of desaturation, which, if left untreated, 
naturally evolves to hypoxemia12. The occurrence of this during airway manipulation in children 
may be accompanied by even more serious complications such as cardiopulmonary arrest (CRP) 
and death11. 
Decreasing oxyhemoglobin saturation to levels less than or equal to 95% induces changes in 
hemodynamic parameters such as systolic index [ratio of heart index (systolic volume x heart rate / 
body surface area) and heart rate], which indicates a reduction in blood pressure. heart function13. 
Data from a five-year tertiary hospital study (12,158 surgeries) document respiratory events 
accounting for 29% of perioperative cardiac arrest in children. This share rises to more than half 
(56%) when analyzing anesthesia-related data. All CRP attributed exclusively to the anesthetic act 
were induction14. 

Another study (10,649 anesthesias) conducted through a questionnaire with data from a period of 
six years points to problems in airway management as the major cause of anesthesia-related CRP15. 
Proper anatomical characteristics may contribute to the occurrence of hypoxemia in perioperative 
children, such as: 1) proportionally large head and tongue; 2) adenoid and tonsil hypertrophy; 3) 
smaller and narrower hypopharynx; 4) higher larynx at neck height; 5) inclined vocal cords, not at 
right angles; 6) inverted U-shaped epiglottis; and 7) smaller airway radius compared to adults, 
which imposes more airflow resistance according to Poiseulle's law (R = 8ƞL / πr4). All these 
factors imply daily challenges to airway manipulation, either during ventilation or during 
intubation16. In infants, airway closure occurs during general anesthesia induction, primarily in the 
anterior-posterior direction, and is uniform throughout the pharynx, which changes in older children 
in whom the epiglottis is the point of greatest narrowing6. 
The physiological characteristics of pediatric patients, such as lower CRF, higher VO2, higher 
carbon dioxide (CO2) production and higher incidence of respiratory complications during the 
induction period when O2 supply is interrupted, also contribute to the decrease in saturation. 
oxygen by hemoglobin9,11,16,17. Age also has a linear correlation with the duration of apnea 
before oxyhemoglobin desaturation, as well as the lower the patient's weight, the higher the 
incidence of severe episodes of the event8,11. The risks of obstruction and desaturation appear to be 
higher in children under three years6. 
One of the strategies used by the anesthesiologist to prevent this complication is pre-oxygenation, 
which offers O2 at levels above those usually breathed by the patient in order to increase their 
stocks. This strategy allows prolonging the time before oxyhemoglobin desaturation9,11,18. In 
theoretical models, O2 body reserves (lung, plasma and hemoglobin) may increase by more than 
two and a half times when the inspired fraction of that gas (FiO2) is equal to 1. This increase is 
mainly at the expense of the alveolar fraction. in CRF, the body's main oxygen reservoir8,17. This, 
associated with VO2 and cardiac output, is responsible for the availability of O2 to the patient8. 

Preoxygenation, despite the benefits, may also contribute to the occurrence of oxyhemoglobin 
desaturation. Microatelectasis and ventilation / perfusion (V / Q) disturbance are documented 
during anesthesia induction under different FiO2. Alveolar recruitment maneuvers and use of end-
expiratory airway pressure (PEEP) can reverse and prevent the occurrence of these events, 
respectively7,8. Other preventive strategies, such as apneic oxygenation, have also been studied, but 
it is not yet known which technique is ideal19,20. 
A variation of noninvasive ventilation, Continuous Positive Airway Pressure (CPAP) is a ventilation 
mode in which the patient breathes spontaneously through a pressurized circuit21. In patients with 
obstructive sleep apnea, in which its use is already well established, benefits such as improved 
sleepiness and severity of the disease, improvement in cardiovascular outcomes, as well as a 
reduction in blood pressure, and additional indirect effects such as an improvement in endurance, 
were evidenced. insulin therapy in non-diabetics22-24. 
From the ventilatory point of view, its benefits are demonstrated by the improvement in alveolar gas 
exchange, minimization of atelectasis formation and increase of both functional residual capacity 
and tidal volume21. Improvements in peripheral oxygen saturation, peak respiratory flow and 
reduction in both frequency and respiratory work have been evidenced in patients during asthma 
attacks25. 
In the pediatric population, CPAP is widely studied in patients with bronchiolitis as an alternative to 
controlled mechanical ventilation due to its effects on small airways (alveolar opening, prevention 
of atelectasis and increased functional residual capacity) 26,27. A study conducted with patients 
between three months and five years of age with respiratory distress also showed a potential benefit 
through reduced respiratory rate28. 
There is evidence that CPAP can be effective in minimizing the deleterious effects of pre-
oxygenation under high FiO2 by maintaining lung volume7. Its use in ventilation during general 

anesthesia induction still requires well-conducted studies to support its routine practice, but research 
in adults shows encouraging results29,30. 
In patients without comorbidities, candidates for major surgery, the longer apnea before 
desaturation and the highest PaO2 values in those who received CPAP during anesthetic induction 
were significant. The use of CPAP also reduced the time to return to normal baseline saturation after 
apnea29. 
The use of CPAP was also related to higher PaO2 and lower carbon dioxide blood pressure values 
(PaCO2) in obese in anesthetic induction. There were no episodes of hypoxemia in these patients, 
unlike those who did not use the continuous positive pressure technique30. 
The aim of this study is to evaluate the effectiveness of CPAP during anesthetic induction in 
increasing apnea time until hemoglobin saturation drops to 95% in children undergoing general 
anesthesia for elective surgery. 
 
Primary hypothesis 
- The use of CPAP in preschoolers' pulmonary ventilation during general anesthesia induction for 
elective surgery delays the occurrence of oxyhemoglobin desaturation during apnea. 
 
Secondary hypotheses 
- Oxyhemoglobin saturation values in pulse oximetry in apneic patients in similar periods during 
anesthetic induction are higher in those using CPAP; 
- Time to recovery of normal oxyhemoglobin saturation levels in pulse oximetry after apnea is 
shorter in patients using CPAP; 
- The frequency of complications (laryngospasm, hypoxemia, bradycardia, cardiopulmonary 
arrest, death) is lower in patients using CPAP. 
General objective 
To evaluate the effectiveness of CPAP during anesthetic induction in increasing apnea time until 
hemoglobin saturation drops to 95% in children undergoing general anesthesia for elective surgery. 

 
Specific objectives 
In children undergoing general anesthesia for elective surgery who will undergo CPAP or standard 
circular circuit ventilation during anesthetic induction, compare: 
PRIMARY OUTPUT: 
The time between onset of apnea and 95% drop in oxyhemoglobin saturation between groups. 
Secondary Outcome: 
Oxyhemoglobin saturation values on pulse oximetry during anesthetic induction at different times 
between groups; 
Time to recovery of oxyhemoglobin saturation levels in pre-apnea pulse oximetry between groups; 
The frequency of complications (laryngospasm, hypoxemia, bradycardia, cardiopulmonary arrest, 
death) between the groups. 
Study Design 
This is a randomized, phase III, parallel clinical trial in pediatric patients undergoing elective 
surgery. 
 
Study site 
The study will be developed in the operating room of the Clinical Hospital of the Federal University 
of Pernambuco (HC-UFPE). 
The HC-UFPE Pediatric Surgery Service performs about 15-20 surgeries per week on an elective 
basis; The team consists of six surgeons and three resident physicians; and has a room in the 
operating room in four weekly shifts where it performs procedures on children from birth to 18 
years. 
 
Study Period 
The study will be conducted from January 2018 to June 2018. 
 
Study Population 

Preschool pediatric patients undergoing elective surgery in the operating room of Hospital das 
Clínicas. 
 
Sample 
 
Sampling 
A non-probabilistic convenience sample will be obtained, composed of preschool children who will 
be submitted to general anesthesia for elective surgery, following the inclusion and exclusion 
criteria of the study. 
 
Sample size 
Sample size calculation was performed using Openepi software, version 3.01 (Dean AG, Sullivan 
KM, Soc. MM. OpenEpi: Open Source Epidemiologic Statistics for Public Health, Version. 
Www.OpenEpi.com, updated 2013/04/06, accessed 2017/07/11), using difference of means. The 
first parameter used was the mean time in apnea that patients exposed to the intervention took to 
achieve a pulse oximetry oxygen saturation of 95% (166 ± 47 seconds) 20. The second parameter 
was the average time in apnea that patients not exposed to the intervention took to reach a pulse 
oximetry oxygen saturation of 95% (131 ± 39 seconds) 20. Considering a significance level of 5% 
and a power of 90%, 64 patients (32 in each group) will be needed. However, with possible losses 
due to post-randomization exclusion (around 10%), this number will be increased to 72 (36 in each 
group). 
 
Randomization Procedure 
The randomization table will be generated on the computer using the Random Software Allocation 
program. After randomization, opaque envelopes numbered sequentially from 1 to 72 will then be 
prepared according to the random number table. The allocation concealment will be respected. 
 
Criteria and procedures for selecting, capturing and following participants 
 
Inclusion criteria 
Preschool children; 

ASA I or II; 
Children undergoing general anesthesia for elective surgery; 
 
Exclusion Criteria 
Pre-existing parenchymal lung disease; 
Cyanotic or oxyhemoglobin-saturated children less than 95% before anesthetic induction; 
Recent history (<4 weeks) or duration of upper respiratory tract infection; 
 
Participant Capture and Follow-Up Procedures 
Participants will be captured by an undergraduate student who will not participate in the data 
collection. He will be solely responsible for capturing participants, applying the eligibility criteria 
using a checklist (Appendix 1) and requesting the signature of the IC. This stage will take place at 
the entrance to the operating room where patients and caregivers, coming from the outpatient clinic 
after weighing and measuring, await surgery. Subsequently, it will deliver to the principal researcher 
the envelope referring to the participant, which will contain the group to which he / she has been 
allocated. 
Allocation will be by sequentially numbered, otherwise identical, sealed envelopes, each containing 
a 2 inch by 2 inch paper with a written code that will designate the intervention group or the 
comparative group. There will be no detectable differences in size or weight between intervention 
group envelopes and comparative group envelopes. Envelopes will be opaque and opened 
sequentially only after the patient information assigned to them has been written to them. The 
envelope opening will occur before the patient enters the operating room so that the study setting 
can be set. 
The lead researcher will be responsible for the entire procedure, along with the anesthesiologist 
responsible for the surgery. Data collection in turn will be performed by a student of scientific 
initiation responsible only for data collection without knowledge of the group to which the patient 
will be allocated (CPAP system will be selected before the student enters the room for collection). 

A flowchart (CONSORT) will be completed with study progress throughout the phases of a two-
group parallel intervention study (participant selection, intervention allocation, follow-up, and data 
analysis) (Figure 1). 
All medical records of the participants involved in the study will be identified by self-adhesive 
labels containing the research name, registration number, study identification number and the group 
in which it was allocated. 
Terms, Variables and Concepts 
 
Control Variables (for sample characterization) 
Age 
Weight 
Height 
Sex 
Physical state according to ASA 
Surgery type 
 
Independent Variable 
CPAP Usage 
 
Dependent Variables 
Time between onset of apnea and 95% drop in oxyhemoglobin saturation (Time 1); 
Oxyhemoglobin saturation on pulse oximetry during anesthetic induction at different times; 
Frequency of complications: laryngospasm, hypoxemia, bradycardia, cardiopulmonary arrest, death; 
Time to recover oxyhemoglobin saturation levels in pre-apnea pulse oximetry (Time 2); 
Procedures, tests, techniques and exams 
 
Performing Anesthesia: 
Patients selected for the study will be admitted to the operating room and will receive regular 
monitoring (cardioscope, oximeter, noninvasive blood pressure and capnography). 

Inhalation induction will be with 8% sevoflurane, 60.5% inspired oxygen fraction under fresh gas 
flow of 4l / min (2l oxygen and 2l compressed air) until loss of eyelid reflex. The anesthetic 
concentration will then be reduced to 4%. A face mask coupled to the anesthesia machine will be 
used, fixed to the patient through an elastic band. 
After adequate ventilation is verified through the correct positioning of the face mask and 
capnography curve present, peripheral venous access with venous catheter number 20, 22 or 24G 
will be obtained for hydration and propofol infusion at a dose of 3.5mg / kg to induce apnea in 
patients in both groups. 
 
CPAP Realization 
Patients will be submitted soon after monitoring the technique described on the envelopes delivered 
at the entrance to the operating room. 
In the CPAP group, it will be applied to the anesthesia device (Dräger Fabius GS) using a circular 
system. This system consists of two corrugated tubes coupled at one end to a Y-piece, connected to 
the patient's face mask, and at the other end to the anesthesia machine which, in addition to 
providing fresh gas flow, has a carbon dioxide absorber called lime. soda. The latter allows the 
system to be circulated by removing CO2 from the air supplied to the patient, warms and humidifies 
the gas mixture. A pressure relief valve (pop-off valve), which prevents gas loss by the patient-
device system when closed, is an integral part of the anesthesia device. It has several markings 
(0-70cmH2O), is manually manipulated and can be open (0cmH2O), ie without any pressure being 
supplied to the patient's airway or closed. In the closed position, there will be continuous positive 
pressure being delivered to the patient's airway. The pressure that will be used in this group will be 
10cmH2O. 
In the Open System group, the system will remain with the valve in the open position, ie 0cmH2O. 
In both groups, patients will spontaneously ventilate from the outset with the technique defined at 
the time of allocation. 

After the apnea begins, the time will be timed and periodically (every 10 seconds), the 
oxyhemoglobin saturation through the pulse oximeter will be recorded for a maximum time limit of 
five minutes in order to catch a minimum saturation of 95% in both groups. 
The entire anesthetic procedure will be attended by the anesthesiologist who accompanies the 
patient and will be at his discretion as soon as the study is over. 
 
Procedures for data collection 
 
Data Collection Instrument 
Data will be collected using a standard, pre-coded form for data entry into the computer (Appendix 
3). Information on categorical variables will be pre-coded and continuous variables will be 
expressed at their own numerical value and only at the time of analysis will the results of some of 
these be categorized. 
These forms will be properly stored in specific file folders, before and after typing and analysis, 
under the responsibility of the researcher, who will fill them out at different times, before, during 
and after the surgical procedure. 
 
Data collect 
Data will be collected by an independent researcher who will be present in the operating room, fill 
out the form with patient identification data and study variables and will not interfere with the 
anesthetic procedure to be performed. 
The time from the moment of cessation of respiratory movements and decay of the capnography 
curve will be timed. The measurement will take place until the pulse oximetry is recorded at 95%. 
Assisted ventilation will then be instituted (in the Open System group, the pop-off valve will be 
manually closed to 10cmH2O). At this time, there will be a new timing of the time until pulse 
oximetry reading of the value of 100% or the value obtained immediately before the beginning of 
apnea. 
 
Data Processing and Analysis 

 
Data Processing 
Typing in the specific database created in the excel program will be performed twice, at different 
times and by different people, obtaining at the end a listing to correct any typing errors, under the 
supervision of the researcher himself. 
In case of inconsistencies or lack of data when the listings are reviewed, the corresponding archived 
forms will be consulted, according to the patient's registration number. 
Upon completion of the entry of all forms in the database, the final revision will be performed and 
the missing data will be completed by the above mentioned processes. The definitive database thus 
created will then be used for statistical analysis in the STATA program, being also submitted to tests 
of consistency and cleaning of the information, generating backups. 
Data analysis 
Data analysis will be performed by the researcher and the responsible statistician (supervised by her 
advisor), using the STATA program. 
Descriptive statistical analysis will be performed through measures of central tendency and 
dispersion for quantitative variables and frequency distribution for qualitative variables. For 
comparison of paired samples, a non-parametric method, Wilcoxcon's t-test will be used. 
Student's t-test will be used for two independent samples, previously considering the Kolgomorov-
Smirnoff normality test for each sample, and for non-normality, the nonparametric Mann-Whitney 
U test will be used. Quantitative variables according to the time of their performance will be used 
analysis of variance for repeated units (ANOVA), if they present a normal distribution, or 
Wilcoxcon if normality is not present. For categorical variables, Fisher's exact test or Chi-square 
will be used when necessary. 
 Relative Risk and its 95% confidence interval, in addition to the Number Needed to Treat and 
Benefit (NNT) or the Number Needed to Treat or Harm (NNH) where relevant, will also be 
calculated. 

 
Ethical aspects 
The research will respect human rights and the principles of bioethics (Autonomy, Non-
Maleficence, Charity, Justice and Equity). Confidentiality and confidentiality in the collection and 
archiving of collected data will be respected. 
The terms of National Council of Health Resolution No. 466 of December 12, 2012 for human 
research will be followed as well as the Declaration of Helsinki. In addition, the project will be 
submitted to the Research Ethics Committee of the proposing institution, the data will only be 
collected after such submission and approval of the committee, and the children of the study will 
only be included after the parents or guardians have signed the free and informed consent form. 
Clarified (IC, Appendix 2). 
The study will be registered in ClinicalTrials.gov and will not offer any additional risks or 
discomforts beyond those inherent to the anesthetic-surgical procedure itself, as well as no adverse 
effects that contraindicate the use of CPAP during induction have not been reported in the literature. 
In contrast, the few existing studies report respiratory improvement with the use of this intervention. 
All research procedures will be performed by trained and qualified professionals for both pediatric 
anesthesia and CPAP. 
The informed consent form (Appendix 2) will provide the guardians with all information regarding 
the advantages and disadvantages of using both techniques; emphasize that no procedures no longer 
routinely performed by the team will be performed; It will include the right to refuse to participate 
in the study, as well as the guarantee of assistance to those who do not accept it, without 
compensation from the institution or from the researchers. They will undertake to publish the study, 
regardless of the results obtained. 
 
Interest conflicts 
This research will be free of conflict of interest, private or institutional. There will be no funding 
from the pharmaceutical industry or representatives of any research object used. 

Informed Consent Form 
We request your permission to invite your child ________________ {or minor under your 
responsibility} to participate, as a volunteer, in the Continuous Positive Airway Pressure during 
General Anesthesia Induction survey. FOR ELECTIVE PEDIATRIC SURGERY: RANDOMIZED 
CLINICAL TEST. Before you can decide whether or not to participate, you need to know the 
benefits, risks and consequences of your participation. 
This document is called the Informed Consent Form (ICF) and is named after you should only 
participate in the research after you have read and understood this statement. Please read the 
information carefully and talk to the responsible researcher and research team about any questions 
you may have. If there is a word or term you do not understand, talk to the person responsible for 
obtaining this consent for further clarification. If you prefer, talk to your family, friends, and 
medical staff before making a decision. Once you have received all the information, you may 
provide your consent by initialing and / or signing both copies, one from the responsible researcher 
and one from the research participant. 
If you do not agree, there will be no penalty for you or the child you are responsible for, and it will 
be possible for you to withdraw consent at any time, also without any penalty. 
This is a research, which is the responsibility of researcher Jayme Marques dos Santos Neto, who is 
an anesthetist and is studying a technique to help the breathing of children during surgery. The 
researcher's address is: Avenida Boa Viagem, 306 apt. 701, Pina, Recife-PE Zip Code 51011-000; 
telephone (81) 996212977. Dr. Jayme is doing a Master's dissertation and is being advised by also 
Anaesthesiologist Dr. Flávia Augusta of Orange Lins da Fonseca e Silva, Phone 81994197979, 
email orangeflavia@gmail.com 
RESEARCH INFORMATION: 
Your child is being asked to participate in research that will study the effect of a breathing aid 
during the onset of anesthesia. We call this technique Continuous Positive Pressure (CPAP). 

For the child to have surgery, he needs to receive general anesthesia. To do this, she breathes using a 
silicone or plastic mask that is attached to the anesthesia machine. The gas that comes from the 
anesthetic device contains the medicine that makes the child sleep. This technique is popularly 
known as “smelling”, but is actually General Anesthesia, and is commonly used in virtually all 
anesthesia in children. CPAP is done the same way. The only difference to usual ventilation is that 
in CPAP the anesthesia machine provides a pressure that can help (is what we want to find out) 
better breathing. 
Two groups will be formed in which one child will receive CPAP and the other child will receive 
usual ventilation. We don't know which group your child will be in. Her participation is not 
required. The aim of this project is to know if CPAP at the beginning of anesthesia improves the 
child's safety and if the oxygen in her blood remains at normal levels any longer. 
Your child's participation ends as soon as she returns to the initial condition in the study when her 
surgery will then be performed. We want to make it clear that this is not a new method that is 
already being used and is considered a safe technique. In previous studies, no side effects or 
complications were found. 
It is hoped that as a result of this study, the use of CPAP at the onset of anesthesia may be 
increasingly encouraged, improving the quality of anesthetic care. All anesthesia will have the 
participation of the anesthesiologist responsible for the surgery and the researcher who will be 
present throughout the study period, thus increasing the vigilance over the procedures performed on 
your child. 
Undesirable effects are likely to occur in any research study, such as embarrassment in signing this 
term, despite all possible precautions, and can happen without your own or the researchers' fault. If 
your child experiences undesirable effects such as associated harm from your participation in this 
study, immediate and full professional assistance will be provided. 

Possible advantages for your child are more oxygen in her blood, less chance of problems at the 
beginning of anesthesia, increased safety time for her if any problems also occur at the beginning of 
anesthesia and faster recovery if she stops breathing. 
The information of this research will be confidential and will be disclosed only in scientific events 
or publications, with no identification of volunteers, except among those responsible for the study, 
ensuring confidentiality about the participation of the volunteer. The data collected in this research, 
through forms, will be stored in archive folders, under the responsibility of the researcher, at the 
address informed above, for a period of at least 5 years. 
You will not pay anything and will not receive any payment for him / her to participate in this 
research, as it must be voluntary, but compensation is also guaranteed in cases of damage, evidently 
resulting from his / her participation in the according to a judicial or extra-judicial decision. If 
necessary, expenses for participation will be borne by the researchers (reimbursement for 
transportation and food). 
If you have any questions regarding the ethical aspects of this study, you may consult the IMIP 
Research Ethics Committee Involving Human Beings at: Rua dos Coelhos, 300, Boa Vista. IMIP 
Research Directorate, Orlando Onofre Administrative Building, 1st Floor tel: 2122-4756 - Email: 
comitedeetica@imip.org.br. The CEP / IMIP is open from Monday to Friday, from 07:00 to 11:30 in 
the morning and from 13:30 to 16:00 in the afternoon. 
________________________________________________________________ 
Researcher's signature 
CONSENT OF THE RESPONSIBLE FOR THE PARTICIPATION OF THE VOLUNTEER 
I, _____________________________________, CPF_________________, the undersigned, 
responsible for _______________________________, authorize your participation in the study. I 
was duly informed and informed by the researcher about the research, the procedures involved in it, 

as well as the possible risks and benefits arising from his / her participation. I have been assured 
that I can withdraw my consent at any time without this leading to any penalty or interruption of 
your follow-up care for me or the minor concerned. 
Place and date __________________ 
Signature of Responsible: __________________________