Author's response to reviews
Title: Effectiveness of heat and moisture exchangers in preventing ventilatorassociated pneumonia in critically ill patients: a meta-analysis
Authors:
Mayra Gonçalves Menegueti (mayra_menegueti@yahoo.com.br)
Maria Auxiliadora-Martins (mam_martins@hotmail.com)
Altacílio Aparecido Nunes (altacilio@fmrp.usp.br)
Version: 1 Date: 28 August 2014
Author's response to reviews: see over
In order to make it easier to Editor/Reviewer to identify the changes performed,
we have highlighted all changes using yellow tags.
Editor's Comment:
In addition, it will be important for you to consider estimating the
appropriate sample size required to demonstrate an effect of heat and
moisture exchanger on ventilator associated pneumonia.
You will
probably agree with my conclusions that your study is under-powered to
arrive at a rigorous conclusion. Therefore, your conclusions must be
changed to address this limitation. You can discuss in your discussion
section the sample size required to identify a 5 % difference in the
incidence of VAP In addition, it will be required to include the true
incidence of VAP (not just the estimated odds-ratios) for all studies
included in this analysis.
Considering a 5% reduction in the occurrence of VAP among patients who used
respectively, HH (16%) and HME (11%), with a significance level of 5% and a
statistical power of 80%, the minimum sample per group would be 731 subjects.
In the present meta-analysis, it was evaluated studies with 953 subjects in the
HH group and 1077 in the HME group.
Reviewer’s #1Comment:
Introduction
Para1, line 1. “still is” should be “remains to be”
We are thankful to the Reviewer #1comment. We have changed the words as
suggested.
Para1, line 2. “period” should be “duration”
We have changed the word as suggested.
Para1, lines 3-4. “In the particular case of Brazil...”, “...constitutes...”
should be “is”.
We have changed the word as suggested.
Para1, line 5. “...which is associated with increased hospital costs...”. The
difference between association and causality should be made clear here.
We have changed the phrase as suggested.
Para1, lines 7-8. “...commonly named ventilator associated pneumonia
(VAP)”. If you’re going to use acronyms, you need to spell them out fully
at the beginning, not re-word them.
We apologize for this mistake and we have already done the correction as
requested: ventilator-associated pneumonia (VAP).
Para1, final line. Please qualify what constitutes a “high-risk situation”.
In order to solve this query, we have inserted the following sentence: “Mortality
due to VAP varies between 24 and 50% and may reach rates as high as 76% in
patients with comorbidities such as COPD, diabetes and other chronic lung
diseases.”
Para2, lines 1-6. Please provide references for all these claims.
Regardless of how common sense they may seem.
We have inserted two references as requested:
7-Branson RD, Chatburn RL. Humidification of inspired gases during
mechanical ventilation. Respir Care 1993; 38:461-68.
8-Hess DR, Kacmarek RM. Essentials of mechanical ventilation. New York:
McGraw-Hill, 1996; 33-40.
Para3, all lines. This whole paragraph is speculative without the presence
of any references.
We have inserted three references about this topic as requested:
8)Hess DR, Kacmarek RM. Essentials of mechanical ventilation. New York:
McGraw-Hill, 1996; 33-40.
9)Craven DE, Goularte TA, Make RJ. Contaminated condensate in mechanical
ventilator circuits: a risk factor for nosocomial pneumonia? Am Rev Respir Dis
1984; 129:625-28.
10)Martin C, Thomachot L, Quinio R, et al. Comparing two heat and moisture
exchangers with one vaporizing humidifier in patients with minute ventilation
greater than 10 L/min. Chest 1995; 107:1411-15.
Methods
Data analysis and statistical methods
Please keep the past/future tense consistent throughout this section. You
can either use past:
“...helped to evaluate...” (line 2), “...considered two outcomes...” (line 3),
“...were used...” (line 6),
or future:
“...will be graphically represented by...” (line 11).
In order to solve this problem, we have changed “will be graphically represented
by” to “was graphically represented by “.
Results
Figure 4 legend:
“...did not afford...” is a bit clumsy. “...was not associated with different
mortality rates/risk of mortality” would be clearer.
We have changed the words as suggested.
Discussion
Para3, line 1. “verified” implies a superior conclusion to “association”.
Just use “demonstrated” here.
We have changed the words as suggested.
Para3, lines11-12. “...concerning the ventilator probe diminished, which...”
I don’t understand this sentence. Did the technical issues diminish? Are
you trying to say that HME are more simple to use and maintain, therefore
requiring reduced nursing staff interventions compared to HH, and this
results in lower costs? Also – the difference of 58 cents per patient, per
day, is not that remarkable. As you start to address in the next paragraph
(Para4, whole paragraph), there are increased risks associated with HME,
when compared to HH. It was be
interesting to see some discussion of the health economics associated
with these costs.
We apologize for these errors. We have corrected all of them in the revised
version of the manuscript. We have rewritten this sentence as requested:
“In addition, it may have some disadvantages using HH; such as high
maintenance costs and mechanical malfunction of the humidification and
mechanical ventilator apparatus, and overheating of the inspired gases. These
problems could be avoided by using HME [10,11,12,17]. ” We have also
included three references about this topic:
8)Hess DR, Kacmarek RM. Essentials of mechanical ventilation. New York:
McGraw-Hill, 1996; 33-40.
9)Craven DE, Goularte TA, Make RJ. Contaminated condensate in mechanical
ventilator circuits: a risk factor for nosocomial pneumonia? Am Rev Respir Dis
1984; 129:625-28.
10)Martin C, Thomachot L, Quinio R, et al. Comparing two heat and moisture
exchangers with one vaporizing humidifier in patients with minute ventilation
greater than 10 L/min. Chest 1995; 107:1411-15.
Para9, lines 1-3. This is unclear. Please re-word.
We apologize for this confusing information. We are thankful to the Reviewer
and we have decided to exclude this statement below:
Some directions for future research should be drawn out from current metaanalysis. The adequate sample, comprehensive side effects should be
considered in future research. Furthermore, studies aimed to compare HME
and HH should be conducted to evaluate the clinical and economic efficacy of
both. Finally, studies should use standardized diagnosis criteria, such as those
of CDC (Centers for Disease Control and Prevention).
Reviewer’s #2 Comment:
1. In line 97 the authors suggest that patients may acquire VAP by
aspirating
condensation
in
the
ventilator
circuit
when
using
a
conventional humidifier. Although this may be true, it may be more likely
to occur when pieces or hardened secretions adhering to the inner wall of
the endotracheal tube become dislodged and enter the respiratory tract.
This condition is more likely to occur when using a HME because of the
lower relative humidity generally associated
with HMEs as compared to conventional humidifiers.
We are thankful to the Reviewer #2comment.
In fact, the occurrence of the aspiration the condensation of water is more likely
to occur when using a HH. When using HME, which may occur is the occlusion
of the tube by hardened secretions. We would like to clarify this sentence and
we have rewritten it as requested:
“Patients may acquire VAP by aspirating the condensation of water (ie,
overhumidification) that originates in the ventilator circuit upon use of a
conventional humidifier.” We have also inserted three references about this
topic:
8)Hess DR, Kacmarek RM. Essentials of mechanical ventilation. New York:
McGraw-Hill, 1996; 33-40.
9)Craven DE, Goularte TA, Make RJ. Contaminated condensate in mechanical
ventilator circuits: a risk factor for nosocomial pneumonia? Am Rev Respir Dis
1984; 129:625-28.
10)Martin C, Thomachot L, Quinio R, et al. Comparing two heat and moisture
exchangers with one vaporizing humidifier in patients with minute ventilation
greater than 10 L/min. Chest 1995; 107:1411-15.
2. Most heated humidifiers offer the option of utilizing heated inspiratory
and/or expiratory limbs of the ventilator circuit. This would of course
decrease/eliminate condensation in the circuit. Use of heated circuits in
the studies reviewed is not mentioned.
Only one study (Boots et al, 2006) have compared the incidence of ventilatorassociated pneumonia (VAP) in patients using circuits humidified with a
hygroscopic heat-and-moisture exchanger with a bacterial viral filter (HME) or
hot-water humidification with a heater wire in both inspiratory and expiratory
circuit limbs or the inspiratory limb only. The results showed that different
humidification strategies used in this study there was not impact on the
character of respiratory secretions or the incidence of VAP.
3. Use of a HME requires that the device be removed during
administration of aerosolized medication either by metered dose inhaler
(HME) or standard medication nebulizer. This results in disruption of the
patient circuit every time an aerosolized medication is delivered, which
commonly occurs every 4 to 6 hours and may be even more frequent. It is
not clear whether or not any of the patients in these studies received
aerosolized medication.
Only one study (Kollef et al) reports the use of aerosol and showed no
difference between groups.
4. There is no mention of the temperature of inspired gas nor the relative
humidity associated with the conventional heated humidifiers. If this data
is available it should be provided as both may contribute the amount of
absolute humidity in the inspired gas.
The temperature of inspired gas ranged from 31 to 37ºC when the HH was
used.
5. Frequency with which the HMEs were changed should be reported if
available. Prolonged use may result in decreased performance. More
frequent changes result in unnecessary disruption of the patient ventilator
circuit which may increase the likelihood of developing VAP.
In most studies the change of HME was every 24 hours according to
manufacturer's recommendation. Only in two studies (Lorente et al and
Lacharade et al) the change was every 48 hours. We have inserted this
sentence in the discussion section.
6. Ventilator circuits are generally not changed unless there is a specific
reason to do so (grossly soiled, malfunction, etc.). Any variations to this
practice should be reported if available.
There was no routine replacement of the circuits. Only one study by Martin
(1990), circuits were changed every 48 hours. Probably because at that time
there was still no evidence of the need for routine replacement
7. In line 225 the authors correctly identify tube occlusion as the most
probable adverse effect associated with HMEs. However, they fail to
identify partial tube occlusion which likely occurs in almost all cases
where an HME is used. This results in a decrease in the inner diameter of
the tube, increasing the work of breathing and potentially prolonging the
time on mechanical ventilation. Prolonged time of mechanical ventilation
may be associated with a greater tendency to develop VAP.
In most studies the occlusion was defined as the inability to pass a suction
catheter (10 gauges of external diameter) into the trachea. Only one study
(Roustan et al) cites six episodes of partial occlusion and three episodes of total
occlusion. We have inserted this information in the discussion section.
Version: 2 Date: 18 Semptember 2014
Author's response to reviews: see over
In order to make it easier to Editor/Reviewer to identify the changes performed,
we have highlighted all changes using yellow tags.
Editor's Comment:
You need to acknowledge that the power of your study was not sufficient
to definitely exclude an associate between heat and moisture exchangers
and VAP.
We are thankful to the editor. I have changed the manuscript and included the
statement below:
“Considering a 5% reduction in the occurrence of VAP among patients who
used respectively, HH (16%) and HME (11%), with a significance level of 5%
and a statistical power of 80%, the minimum sample per group would be 731
subjects. In the present meta-analysis, it was evaluated studies with 953
subjects in the HH group and 1077 in the HME group. However there are some
potential limitations should be considered. Firstly, some studies were not
calculated sample size and were not described the randomization procedure.
Secondly, in two studies patients were excluded after randomization. Thirdly,
two studies were non-blinded. Finally, the definitions of VAP varied in some
included studies. Thus other double-blind studies, randomized controlled should
be performed to definitely exclude an associate between heat and moisture
exchangers and VAP.”
In order to give the relevant information to the Journal's readers, please
provide a table that shows the total number of VAP in each study in each
group.
The table 3 showed the number of VAP in each group. We have prepared the
improvement this table, including the number of VAP in all the studies.
You must change your conclusion statement and discuss the limitations
in a transparent fashion.
In order to improve and clarify the limitations of the study, we have inserted the
limitations of the study and changed the conclusion: “Current meta-analysis was
not sufficient to definitely exclude an associate between heat and moisture
exchangers and VAP. Despite the methodological limitations found in selected
clinical trials, the current meta-analysis suggests, with some degree of
uncertainty, that HME does not decrease VAP incidence or mortality in critically
ill patients and therefore, further clinical trials with greater methodological rigor
and adequate sample size should be performed comparing HH to HME in the
incidence of VAP and other important outcomes such as mortality. Is important
to highlight that, institutions routinely using HME should be aware of obstruction
events and cases of hypercapnia and hypothermia, because some studies have
described their occurrence.”
Version: 3 Date: 30 Semptember 2014
Author's response to reviews: see over
In order to make it easier to Editor/Reviewer to identify the changes performed,
we have highlighted all changes using yellow tags.
You mentioned that your power would be sufficient to identify a 5 per cent
difference in occurrence rate of VAP, a statement that can be easily
misinterpreted. Please clarify in another revision that the proposed
difference between 16 per cent and 11 per cent in the incidence of VAP in
fact represents a >30 per cent decrease in VAP by the intervention under
consideration - one could argue that it is unlikely to assume that a heat
and moisture exchanger decreases VAP incidence by more than 30 per
cent.
We are thankful for this comment. We agree with your argument and we
have change the manuscript, as follow:
“Considering a 30% reduction in the occurrence of VAP among patients who
used respectively, HH (16%) and HME (11%), with a significance level of 5%
and a statistical power of 80%, the minimum sample per group would be 731
subjects. In the present meta-analysis, it was evaluated studies with 953
subjects in the HH group and 1077 in the HME group, thus this review presents
a sufficient sample size to detect this difference.
However there are some
potential limitations should be considered. Firstly, the sample size was sufficient
to detect a 30% reduction in VAP rates; the power of the study was not sufficient
to identify more modest reductions, although smaller reductions could still be
important from a clinical perspective.”
We would like to thank the members of the BMC Anesthesiology for
your attention in revising this manuscript and hope that it is now compatible with
the high quality of the prints from the BMC Anesthesiology and that the
revised version is now acceptable for publication.
Best regards,
Mayra Gonçalves Menegueti, RN, MS
Corresponding Author