Alveolar Hypoventilation Resulting in Hypoxemia Clinical Trial
Official title:
Assessment of Capnography in Monitoring Patients During Nurse Administered Deep Sedation With Propofol
Rationale: The current standard of respiratory monitoring for patients during deep sedation
is continuous pulse oximetry with visual assessment of the patient. Clinical research has
demonstrated that depressed respiratory activity is a principal risk factor for hypoxemia
during sedation. Capnography may provide early detection of alveolar hypoventilation before
hypoxemia has occurred in nonintubated patients and thereby improve patient safety during
sedation.
Objective: At the Centre for Contraception, Sexuality and Abortion Leiden, abortion
procedures are performed under deep sedation using propofol. Patient's monitoring is
performed by nurses qualified in patient sedation management, using pulse oximetry and their
clinical judgement. The aim of this study is to examine the effectiveness of capnography in
early detection of alveolar hypoventilation during deep sedation in comparison to standard
monitoring with pulse oximetry in abortion procedures.
Study design: This protocol describes a prospective, open, randomized controlled trial with
two study arms. All patients receive standard care of monitoring performed by the medical
staff. The study investigates whether capnography prevents patients from having respiratory
events during deep sedation in abortion procedures by early detection and therapy. Patients
randomized to the standard care group receive standard of respiratory monitoring using pulse
oximetry. In the capnography arm, respiratory monitoring is performed with pulse oximetry
and capnography.
Study population: The study population comprises female patients (≥ 18 years) undergoing
abortion procedures during first or second trimester pregnancies. Abortion procedures are
performed until 22 weeks of gestational age.
Capnography: In addition application of capnography during deep sedation with propofol is
performed. Before the trial starts, all nurses qualified in patient sedation management and
abortion doctors will be trained in assessment of capnography. In the capnography arm,
patients' breathing is additionally monitored with capnography. If alveolar hypoventilation
is detected medical staff will intervene by arousing the patient, performing chin lift,
repositioning the head, provision of oxygen, or abandon from giving additional propofol.
These interventions represent the standard of care currently used by the clinical staff to
respond to hypoventilation and hypoxemia.
Main study parameters/endpoints: The primary outcome is the occurrence of oxygen saturations
to ≤90% in the population, as measured by continuous pulse oximetry. Secondary study
outcomes include occurrence of oxygen saturations < 80%, dose of administered propofol,
arousal or movement of the patient during the procedure, airway interventions, early
termination of the procedure due to respiratory problems, episodes of bradycardia, and
administration of atropine.
Nature and extent of the burden and risks associated with participation, benefit and group
relatedness: The risks related to the conduct of this study are negligible and the burden
minimal. Patients in both groups receive the current standard of care. Patients randomized
in the capnography group could get benefit from the addition of capnography to the
monitoring by early detection of alveolar hypoventilation. Capnography is a noninvasive
measurement by means of a cannula under the nose, which before the sedation may tickle, but
during sedation no inconvenience is expected.
1. INTRODUCTION AND RATIONALE Since sedation is increasingly administered by
non-anesthesiologists, patient safety during sedation became of increased interest by
the Joint Commission for Accreditation of Healthcare Organisations (JCAHO). The current
standard of respiratory monitoring for patients during sedation is continuous pulse
oximetry with visual assessment of the patient. Clinical research has demonstrated that
hypoxemia, secondary to depressed respiratory activity, is a principal risk during
sedation. Microstream capnography is a relatively new technology for carbon dioxide
(CO2) monitoring. The technique is based on emission of selective infrared wavelengths
exactly matching for CO2 absorption. Due to this efficient and selective emission
process only small samples of CO2 are necessary to detect alveolar hypoventilation, and
accuracy is maintained with a low flow sample rate. Therefore, capnography can provide
more useful information on the frequency, effectiveness and regularity of ventilation,
than pulse oximetry during procedures accomplished under deep sedation. According to
previous reports capnography provides early detection of alveolar hypoventilation
before hypoxemia has occurred in nonintubated patients and thereby can improve patient
safety during sedation.
This study will provide new information on the efficacy of capnography for early
detection of hypoxemia during nurse-administered propofol sedation in adults. Previous
studies, involving a paediatric randomized study and a study in adult gastrointestinal
endoscopy, were outcome studies with capnography in patients sedated with midazolam in
combination with fentanyl or meperidine.4 5 Therefore, we will assess the efficacy of
interventions based on capnographic monitoring of respiratory function in
nurse-administered propofol sedation. In previously conducted studies independent
observers monitored the capnographic display and prompted the medical team of the
changes in respiratory activity. In the following clinical trial we will examine normal
practice by assessment of the capnogram by the nurse qualified in sedation management.
2. OBJECTIVES At the Centre for Contraception, Sexuality and Abortion (CASA) Leiden
abortion procedures are performed under deep sedation using propofol. These procedures
are not attended by an anesthesiologist and patient's monitoring is performed by nurses
qualified in patient sedation management, using pulse oximetry and their clinical
judgement. Supplementary oxygen is not routinely given.
The purpose of this study is to investigate the use of capnography to improve patient
safety during deep sedation. This study examines the effectiveness of capnography in
early detection and therapy of alveolar hypoventilation during deep sedation in
comparison to standard monitoring with pulse oximetry in abortion procedures. The
randomized controlled trial determines whether utilizing capnography in women
undergoing deep sedation with propofol (monotherapy) for abortion procedures will
provide early detection of suboptimal ventilation and reduce hypoxemia. Unlike previous
studies we are determined to investigate daily practice when nurses qualified in
sedation management assess capnography instead of an independent observer assessing
capnography. Therefore, all nurses qualified in patient sedation management and
abortion doctors will be trained in assessment of capnography before the trial starts.
The implications of this study for monitoring deep sedation may be generalized to all
healthy patients having minimal invasive procedures, particularly when a trained
anesthesiologist is not in attendance.
3. STUDY DESIGN This protocol describes a prospective, open, randomized controlled trial
with two study arms. All patients receive standard care of monitoring performed by the
medical staff. The study examines whether capnography prevents patients from having
respiratory events during deep sedation in abortion procedures.Patients randomized to
the standard care group receive standard of care using pulse oximetry. In the
capnography arm, respiratory monitoring is performed with pulse oximetry and
capnography. If the capnogram indicates sub-optimal ventilation and/or apnea, denoted
as a flat line on the capnometer for ≥ 15 seconds, a respiratory rate ≤ 6, or a
end-tidal CO2 > 50 mmHg, medical staff will intervene by arousing the patient,
performing chinlift or jawthrust, abandon from giving additional propofol, or provision
of oxygen. The nurse qualified in sedation management will assess capnography him/
herself. Medical staff and patients are not blinded for the allocation assignment and
the study has an open design.
4. STUDY POPULATION 4.1 Population Participants are recruited at the Centre for
Contraception, Sexuality and Abortion Leiden, the Netherlands. The study population
comprises female patients (≥ 18 years) undergoing abortion procedures during first or
second trimester pregnancies.
4.2 Inclusion criteria Patients were considered for enrolment if they fulfil all of the
following inclusion criteria: age 18 years or older, abortion procedures performed
until 22 weeks of gestational age, American Society of Anaesthesiologists (ASA) classes
I to II, and ability (mental competence) to give informed consent.
4.3 Exclusion criteria Exclusion criteria were inability to provide informed consent,
history of allergic reactions to propofol, soybeans or egg proteins, American Society
of Anaesthesiologists (ASA) classes III- V, sleep apnea syndrome, and seizure
disorders.
4.4 Sample size calculation The sample size calculation for the prospective randomized
controlled trial is based on a comparison of two proportions. The proportion of
patients developing hypoxemia during sedation is reported between 47% and 51% in
observational studies.1 2 Qadeer et al. reported a reduction of hypoxemia (saturation
<90%) with additional capnography monitoring from 69% to 46% and Lightdale et al.
reported a reduction of hypoxemia (saturation <95%) in children from 24% to 11%.4 5
Based on an observation of daily practice in 58 patients at the CASA clinic Leiden
hypoxemia (oxygen saturation < 90%) was recorded in 12 patients, corresponding to an
incidence of 20.7%. To show a decrease in hypoxemia from 20% to 10% with a significance
level of 0.05 and a power of 0.80, 219 patients are required within each arm, yielding
440 patients to be included in total. Give the annual number of 1600 patients and
expecting a participation rate of 60%, we expect to include these patients within a
period of 24 weeks.
5. METHODS 5.1 Study parameters/endpoints
5.1.1 Main study parameter/ endpoint The primary outcome is the occurrence of oxygen
saturations to <90% in the population, measured by continuous pulse oximetry.
5.1.2 Secondary study parameters/endpoints Secondary study outcomes include occurrence of
oxygen saturations to <80%, total administered propofol dose, airway interventions
(repositioning the head, chinlift, supplemental oxygen, bag-mask ventilation), problems
during the abortion procedure (e.g. arousal or movement of the patient), early termination
of the procedure due to respiratory problems, episodes of bradycardia, administration of
atropine.
5.1.3 Other study parameters Carbon dioxide monitoring with capnography will provide the
following parameters: apnea (absence of respiratory activity) denoted as a flat line on the
capnometer for ≥ 15 seconds, abnormal ventilation denoted as a respiratory rate ≤ 6, and
end-tidal CO2 > 50 mmHg (CO2 > 6.7 kPa).
Baseline values are age, height, body weight, duration of pregnancy, American Society of
Anaesthesiologists class, smoking, abuse of alcohol or drugs, and use of soporifics.
5.2 Randomisation, blinding and treatment allocation During the trial patients are randomly
assigned to the capnography group (standard care and monitoring with capnography) or the
control group (standard care) by randomisation. The randomisation is computer-generated and
stratified for each abortion doctor.
Participants are recruited by an independent observer or nurse. The patient and medical
staff will not be blinded to the allocation assignment and also the independent observer is
aware of the randomisation assignment before the start of the procedure.
5.3 Study procedures
- Daily practice at the CASA clinic: If patients opt for an abortion procedure after five
days of statutory reflection they are coming to the clinic with an appointment. Before
any procedure starts, patients have again a conversation with a doctor or nurse about
their decision to have an abortion. If an abortion is inevitable and pregnancy lasts no
longer than 16 weeks, the patient is immediately admitted to the clinic. If an abortion
is inevitable and pregnancy lasts between 16 and 22 weeks, cervical priming with
misoprostol is administered at least 90 minutes before the abortion procedure.
- A routinely performed health questionnaire, blood pressure, heart rate and blood group
determination are performed in preparation for the procedure. Peripheral venous access
is established at the holding area. Baseline characteristics for the study are obtained
by this routinely performed questionnaire including health questions (e.g. weight,
height, and smoking).
- Patients are asked to be a participant for this study by one of the nurses or by the
researcher at the holding area. They receive an information letter and are able to
question the researcher about their participation.
- Before the procedure starts monitoring, including pulse oximetry and blood pressure, is
attached to each patient
- All patients receive standard monitoring with continuous display of pulse oximetry and
heart rate. In the intervention group capnography is measured using a cannula under the
nose connected to the capnograph, Capnostream TM 20, Oridion Medical 1987 ltd. This
capnographic device displays respiratory rate, end-tidal carbon dioxide (ETCO2) levels,
and continuous waveforms.
- All patients are sedated with an initial dose of 100 milligrams (mg) propofol. In
addition 20-50 mg propofol is administered when patient discomfort or lighter levels of
sedation are noticed. The nurse qualified in sedation management determines the doses
of propofol on a previously described sedation protocol for the CASA clinics. Local
anesthesia of the cervix is performed with 10-20 ml lidocaine 1%.
- When the abortion procedure has finished patients are monitored at the recovery area.
If they are fully awake and no extensive bleeding has occurred, they are allowed to
leave the clinic.
5.4 Withdrawal of individual subjects Subjects can leave the study at any time for any
reason if they wish to do so without any consequences. It should however be noted that
patients during sedation no longer have the ability to express their wishes.
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Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention