Critical Appraisal

The effect of ketamine on hypoventilation during deep

sedation with midazolam and propofol
A randomised, double-blind, placebo-controlled trial
Gildasio S. De Oliveira Jr, Paul C. Fitzgerald, Nora Hansen, Shireen Ahmad and
Robert J. McCarthy
European Journal of Anaesthesiology (2014) 31, 654–662

Oleh
Madeline Marpaung

Pembimbing: dr. Riyadh Firdaus, SpAn-K

 Introduction
• Increasing demand for anesthesia care outside the operating room
• Sedation poses major risks  respiratory depression as the main risk
• Beneficial effect of ketamine on airway patency and ventilation in patients
undergoing sedation
• Hypothesis:
– Ketamine would reduce the duration and severity of hypoventilation compared
with isotonic saline
 Methods
• Sample size: 54 pts • Exclusions:

• Inclusions: – History of allergy to ketamine or

propofol
– Women undergoing outpatient
breast lumpectomy under – Chronic use of an opioid or

monitored anesthesia care and benzodiazepine

deep sedation – Pregnancy

– ASA PS I-II
 Preoperative
Assessment of sleep disorder breathing and the risk of sleep apnea

Operating room
• Monitors according to ASA standards
• Transcutaneous carbon dioxide (TCO2) monitor
• Midazolam 2 mg intravenous (i.v.)
• Propofol infusion started at 100 μg kg-1 min-1, titrated 25 μg kg-1 min-1 every
5 min  OASS between 2 and 3

Group 1 (Ketamine), 27 pts Group 2 (Isotonic saline), 27 pts

Ketamine 0.5 mg kg-1 bolus followed by Isotonic saline 0.5 mg kg-1 bolus followed
1.5 μg kg-1 min-1 infusion by 1.5 μg kg-1 min-1 infusion
 Intraoperative
• Different anesthesia provider managing the patient and research nurse for
collecting data
• Lidocaine 2% infiltrated before the surgical incision
• TCO2 level collected electronically, downloaded to a spreadsheet, evaluated
for the total duration of TCO2 above the cut-off by second investigator
• Sedation time calculated
• Respiratory rate, heart rate, systolic and diastolic blood pressure recorded
• Number of airway maneuvers performed recorded

Postoperative
• Time to hospital discharge recorded
• Incidence of psychomimetic side-effects recorded
• Verbal rating score for pain, incidence of nausea or vomiting recorded
APPRAISAL
 Title

Simple, clear, interesting,

study design mentioned

• CONSORT 2010 recommended identification as a randomised trial in the title

 PICO ANALYSIS
P Women, ASA PS I-II undergoing oupatient breast
Patient/Population lumpectomy under monitored anesthesia care and deep
sedation
I Bolus of 0.5 mg kg-1 followed by 1.5 μg kg-1 min-1 infusion
Intervention of ketamine until the end of the surgery
C Bolus of 0.5 mg kg-1 followed by 1.5 μg kg-1 min-1 infusion
Comparison of isotonic saline until the end of the surgery
O Primary: the percentage of the sedation time that the
Outcome participant’s TCO2 was greater than 6.7 kPa
Secondary: the percentage time that the patients’ TCO2
was above 8.0 kPa, the number of patients who did not
exceed a TCO2 more than 8.0 kPa during sedation

Type of Study/Method: randomized clinical trial

 Abstract

• Good abstract
• Lack of information
about:
– blinding
– estimated effect
size of the
primary outcome
– important adverse
events
– source of funding
 Scientific background

• The background is clearly

described

• Based on scientific literature

• Includes a note of the absence

of such trials
 Specific objectives or
hypotheses

• The hypotheses is stated

explicitly
 Trial design

• Stated explicitly

• “This trial was a single center,

parallel-group open clinical
trial with a computer-
generated allocation sequence
randomization (1:1 ratio).”
 Participants

• The eligibility criteria

(inclusion & exclusion) is
described clearly
 Study setting

• University hospital

• In Chicago, USA
 Intervention

• Intervention for both groups are clearly

described
• Drug name, dose, method of administration,
timing and duration of administration
 Outcomes

• Primary and secondary

outcomes are mentioned
clearly
 Sample size

• How sample size

calculated are described
clearly, data from pilot
study is included
 Randomisation:
sequence generation
• Random allocation sequence is
computer-generated
 Randomisation:
allocation concealment
mechanism
• Group assignments were sealed
in sequentially numbered
opaque envelopes
 Randomisation:
implementation
• Person who enroled participants and
obtained informed consent is not stated
• Assignments envelopes were opened by an
investigator not involved with patient care
• Person who prepared the study drug is not
stated
• Person who administered intervention is
blinded
 Blinding

• Participant blinding is
not stated
• Healthcare providers
was blinded
• Data collector was
blinded
 Statistical Methods

• It is not specified which

statistical procedure was
used for each analysis

• No intention-to-treat
analysis due to protocol
violation
 Participant Flow

• Participant flow is
clear
 Baseline Data

• The intervention and control groups look similar at the start of the study
 Outcomes and
estimation
• Outcomes are reported for
each group with confidence
interval provided

• The effect size is not

presented
 Internal Validity
Sampling method not described
Randomization (+)
Validity of Selection: Allocation mechanism (+)
Fairly good Concealment (+)
Inclusion and exclusion criteria are
specific

Randomization (+)
Validity of Bias Control: Base data: equal
Good Inclusion and exclusion criteria are
specific
 Internal Validity

Blinding (+)
Validity of Information:
Good
Measurement bias (-)
Procedure bias (-)

Validity of Data Result analysis (+)

Analysis: Demographic characteristic
Fairly Good analysis (+)
 External Validity
• 1st external validity: limited
– Subjects represent accesible population  technique of sampling is unclear
– Accesible population: women undergoing outpatient breast lumpectomy
under monitored anesthesia care and deep sedation  time and place were
not clearly mentioned
• 2nd external validity: good
– Accessible population represents target population
 Importancy
• Statistically significant
• Clinically might be significant
– The contrasts between the two groups was not mentioned
 Applicability
• Can be done
• Available
• Applicable
 Conclusion
• Valid
• Important
• Applicable
THANK YOU FOR YOUR ATTENTION