Pediatric Anesthesia ISSN 1155-5645
ORIGINAL ARTICLE
Effect of carboxyhemoglobin on postoperative
complications and pain in pediatric tonsillectomy patients
Onur Koyuncu1, Selim Turhanoglu1, Kasım Tuzcu1, Murat Karcıoglu1, Isil Davarcı1, Ercan Akbay2,
Cengiz Cevik2, Cahit Ozer3, Daniel I. Sessler4 & Alparslan Turan4
1 Department of Anesthesiology and Department of Outcomes Research, Tayfur Ata Sokmen Medicine Faculty, Mustafa Kemal University,
Hatay, Turkey
2 Department of Ear Nose Throat, Tayfur Ata Sokmen Medicine Faculty, Mustafa Kemal University, Hatay, Turkey
3 Department of Family Medicine, Tayfur Ata Sokmen Medicine Faculty, Mustafa Kemal University, Hatay, Turkey
4 Department of Outcomes Research, Cleveland Clinic, Cleveland, OH, USA
Keywords
carbon monoxide; carboxyhemoglobin;
tonsillectomy; child; postoperative
complications; pain
Correspondence
Onur Koyuncu, Department of
Anaesthesiology, Tayfur Ata Sokmen
Medicine Faculty, Mustafa Kemal
University, Serinyol street, Hatay 31000,
Turkey
Email: [email protected]
Section Editor: Andrew Davidson
Accepted 25 August 2014
doi:10.1111/pan.12531
© 2014 John Wiley & Sons Ltd
Pediatric Anesthesia 25 (2015) 247–252
Summary
Background: Carbon monoxide (CO) is a product of burning solid fuel in
stoves and smoking. Exposure to CO may provoke postoperative complications. Furthermore, there appears to be an association between COHb concentrations and pain. We thus tested the primary hypothesis that children
with high preoperative carboxyhemoglobin (COHb) concentrations have
more postoperative complications and pain after tonsillectomies, and secondarily that high-COHb concentrations are associated with more pain and analgesic use.
Methods: 100 children scheduled for elective tonsillectomy were divided into
low and high carbon monoxide (CO) exposure groups: COHb ≤3 or
≥4 gdl 1. We considered a composite of complications during the 7 days
after surgery which included bronchospasm, laryngospasm, persistent coughing, desaturation, re-intubation, hypotension, postoperative bleeding, and
reoperation. Pain was evaluated with Wong-Baker Faces pain scales, and
supplemental tramadol use recorded for four postoperative hours.
Results: There were 36 patients in the low-exposure group COHb
[1.8 1.2 gdl 1], and 64 patients were in the high-exposure group
[6.4 2.1 gdl 1]. Indoor coal-burning stoves were reported more often by
families of the high- than low-COHb children (89% vs 72%, P < 0.001). Second-hand cigarette smoke exposure was reported by 54% of the families with
children with high COHb, but only by 24% of the families of children with
low COHb. Composite complications were more common in patients with
high COHb [47% vs 14%, P = 0.0001, OR:7.4 (95% Cl, lower = 2.5upper = 21.7)], with most occurring in the postanesthesia care unit. Pain
scores in postanesthesia care unit and one hour after surgery were statistically
significantly lower in the low-exposure group [respectively, P = 0.020 (95%
CI, lower = 1.21-upper = 0.80), P = 0.026 (95% CI, lower = 0.03upper = 0.70)], and tramadol use increased at 4 h (3.5 (interquartile range:
0–8) vs 6 (5–9) mg, P = 0.012) and 24 h (3.5 (0–8) vs 6 (5–9) mg, P = 0.008).
Conclusion: High preoperative COHb concentrations are associated with
increased postoperative complications and pain.
247
O. Koyuncu et al.
Carboxyhemoglobin and perioperative complications in children
Background
Almost half of the world’s population uses solid fuel
including biomass (wood, crop residues, and animal
dung) or coal for heating and cooking. Because stoves
are usually centrally positioned in homes and often the
only source of heat, families tend to congregate around
them and sleep nearby (1). Proximity to indoor stoves is
problematic because many generate and release pollutants into household air including particulate matter,
organic compounds, trace metals such as mercury, and
carbon monoxide (CO) (2,3). Household air pollution
from indoor combustion of biomass or coal is thought
to be the third major cause of global disease burden,
and especially affects young children (4). Children are
also exposed to CO via second-hand smoke (5). The
prevalence of smoking is 21% (45 million) for adults (6),
and about 10% of nonsmokers are exposed to secondhand smoke in the United States (7). It is almost certain
that both smoking prevalence and exposure of children
is far higher in most developing countries.
Inhaled CO diffuses rapidly across alveolar and capillary membranes, forming a bond with hemoglobin that
is 200 times tighter than with oxygen, resulting in carboxyhemoglobin (COHb) (8). COHb remains in the circulation for hours and is thus a marker of recent exposure
to CO. Chronic exposure to carbon monoxide may lead
to neurotoxicity, cognitive impairment, and visual
impairment; unconsciousness and death occur at COHb
concentrations exceeding 50% (9).
Carbon monoxide exposure also causes inflammation through multiple pathways that are independent
of the pathways to hypoxia (9), and it is these pathways rather than hypoxia per se that cause most complications consequent to exposure. Carbon monoxide
also impairs lung structural and functional development (10). Consequently, forced expiratory volume in
1 s and vital capacity of the lungs are reduced after
chronic childhood exposure (11); asthma and airway
hyperreactivity are common sequellae (12). CO exposure is also pronociceptive via activation of a cGMPPKG signaling pathway (13,14) and may thus enhance
pain sensitivity.
Exposure to environmental cigarette smoke is associated with various respiratory complications in children
(15,16). But the perioperative effect of presumably much
greater CO exposure that results from indoor stoves
remains to be quantified. In a prospective observational
study, we therefore tested the a priori primary hypothesis that there is an association between preoperative carboxyhemoglobin concentration and postoperative
complications during the initial 7 days after pediatric
tonsillectomy surgery. Our secondary a priori hypothe248
sis was that there is an association between carboxyhemoglobin and acute postoperative pain and analgesic
consumption.
Methods
This prospective observational, assessor-blinded study
was conducted at Mustafa Kemal University Hospital.
The work was approved by the Hospital Ethics Committee (number 207, April 2012), and written consent was
obtained from the parents of all enrolled children.
We enrolled 100 American Society of Anesthesiologists Physical Status I–II children scheduled for elective
tonsillectomy under general anesthesia over the course
of 3 months starting August 2013. Patients were
excluded if they were active smokers, had a history of
prematurity, bleeding disorders, hemolysis, severe
pulmonary disease, home oxygen use, chronic pain, or
inpatient hospitalization within the week.
Protocol
Children were premedicated with midazolam hydrochloride 0.6 mgkg 1 orally about 40 min before surgery. A
local decongestant, oxymetazoline (Iliadin, Merck,
Istanbul, Turkey), was applied to the both nasal passages 10 min before surgery. Anesthesia was induced
with sevoflurane 8% and nitrous oxide 70% in oxygen.
After mask induction, an intravenous cannula was
inserted and rocuronium 0.5 mgkg 1 and fentanyl
1 mgkg 1 were given intravenously before tracheal
intubation. Anesthesia was maintained with sevoflurane
2–3% and nitrous oxide 50% in oxygen.
Before surgery, the nasal passages and oropharynx
were aspirated. The same surgeons, using a standardized
snare technique, performed all tonsillectomies. Operations were completed after homeostasis was obtained by
ligation with absorbable suture materials. A moist
throat pack was placed around the endotracheal tube at
the laryngeal inlet to prevent the passive ingestion of
blood. The oropharyngeal cavity was rinsed with a standardized volume of saline solution at room temperature.
Perioperative blood loss was estimated from the volume
in the suction canister after subtracting the volume of
saline solution used, compensating for the increase in
the weight of the throat pack.
At the end of the surgery, neuromuscular block was
reversed with intravenous neostigmine 0.03 mgkg 1
and atropine 0.01 mgkg 1. Anesthesia was discontinued and the tracheal tube was removed in the operating
room when airway reflexes returned. Children free of
postoperative nausea and vomiting were given 100 ml
of water four hours later. PONV was treated with
© 2014 John Wiley & Sons Ltd
Pediatric Anesthesia 25 (2015) 247–252
O. Koyuncu et al.
Carboxyhemoglobin and perioperative complications in children
intravenous metoclopramide (0.1 mgkg 1 for children
<6 years old and 2.5–5 mg for children ≥6 years old).
All children were given 10–15 mgkg 1 intravenous
paracetamol. If pain exceeded a score of two on the
Wong-Baker FACES Pain Rating Scale (17),
0.25 mgkg 1 tramadol was given. Patients were discharged when they had no bleeding, no nausea and vomiting, were able to drink liquids, and had pain scores of
≤2. Patients stayed at least 24 h in the hospital per surgical routine.
and requiring either administration of continuous positive pressure or a neuromuscular blocking agent to
restore ventilation), persistent coughing (duration longer
than 15 s), desaturation (SpO2 < %95), re-intubation,
hypotension (decrease in systolic arterial pressure of
>10 mmHg from baseline), postoperative bleeding, and
reoperation were recorded.
Measurements
Demographic and morphometric characteristics were
recorded. Parents were asked to complete a 7-item questionnaire about the child’s environmental air quality
including major sources of CO, highlighting second-hand
smoke and indoor coal use (Appendix 1). Questions
related to air quality in the questionnaire were based on
a survey from the Healthy Public Housing Initiative (18).
Children’s COHb levels were measured noninvasively
using a CO-Oximeter (Radical-7 Rainbow SET Pulse
CO-Oximeter; Masimo, Irvine, CA, USA) during preintraoperative period (19,20). Roth et al. found a bias
between noninvasive and blood carboxyhemoglobin of
3%, and a precision of 3.3% in a cohort of emergency
department patients. Other studies have also shown that
multiwave pulse-oximetry measures COHb with an
acceptable bias and precision (21–24). An age-appropriate sensor was applied to the child’s hand or foot. In children weighing more than 10 kg, reusable finger sensors
were used, whereas smaller children received disposable
adhesive sensors to insure appropriate fit and measurement according to the manufacturer’s specifications. The
system was calibrated before anesthesia induction.
Parents were asked to identify their child’s pain intensity using the Wong-Baker Faces Pain Rating Scale (17)
upon admission to the postanesthesia care unit; 1, 2, 4,
6, 12, and 24 h after anesthesia ended, and 7 days after
surgery by phone. Specifically, they were told: ‘Each face
is a person who feels happy because he has no pain or
sad because he has more pain; choose the face that best
describes how your child is feeling.’ An anesthetist
blinded to preoperative COHb concentrations queried
patients about postoperative sedation level using Ramsey sedation scale at admission to the postanesthesia
care unit; 1, 2, 4, 6, 12, and 24 h after anesthesia ended.
Heart rate, noninvasive blood pressure, respiratory
rate, and SpO2 were evaluated at admission to the postanesthesia care unit; 1, 2, 4, 6, 12, and 24 h after anesthesia ended; and 7 days after surgery by phone. Side
effects including bronchospasm, laryngospasm (characterized by an inability to ventilate the patient’s lungs
© 2014 John Wiley & Sons Ltd
Pediatric Anesthesia 25 (2015) 247–252
Data analysis
Qualifying patients were divided a prior starting study
into two groups according to COHb concentrations
measured: (i) COHb ≤3 gdl 1 as low group or
(ii) COHb ≥4 gdl 1 as high group (22). For our sample-size analysis, we used data from a pilot of 10 patients
for each group. 50% of patients with high carboxyhemoglobin levels (COHb ≥4 gdl 1) and 20% of the
patients with low carboxyhemoglobin levels (COHb
≤3 gdl 1) had postoperative complications. This ratio
suggested that 30 patients in each group would provide
a significance (a) of 0.05 and a power (b) > 0.80.
Normality was evaluated with the Kolmogorov–
Smirnov test. Continuous data were compared using
Mann–Whitney U-test and Wilcoxon rank sum tests.
Fisher exact test was used to compare categorical
variables. Results are presented as percentages,
means SDs, medians and interquartile range, or numbers as appropriate. Statistical Package for the Social
Sciences (SPSS) version 15.0 (SPSS Inc., Chicago, IL,
USA). P < 0.05 was considered significant.
Results
One hundred consenting patients who fulfilled the entry
criteria were enrolled; all patients completed the entire
study and were included in the final analysis. 36 patients
were in the low-COHb group [mean SD COHb
1.8 1.2 gdl 1]; 64 patients were in the high-COHb
group [6.4 2.1 gdl 1]. Patients with low- and highCOHb concentrations were comparable with respect to
age, height, body weight, ASA physical status, and gender (Table 1).
Indoor coal-burning stoves were reported more often
by families of the high- than low-COHb children (89%
vs 72%, P < 0.001). Second-hand cigarette smoke exposure was reported by 54% of the families with children
with high COHb, but only by 24% of the families of
children with low COHb. There were no statistically significant differences between high and low-COHb groups
in regard to who smoked at home or whether windows
were left open.
The high-COHb group had significantly more postoperative complications [36 (54%)] than the low-COHb
249
O. Koyuncu et al.
Carboxyhemoglobin and perioperative complications in children
Table 1 Baseline characteristics
Table 4 Postoperative pain scores
COHb ≤3 gdl
(n = 36)
Age (year)
Height (cm)
Weight (kg)
ASA physical status (I/II)
Sex (M/F)
COHb (gdl 1)
1
72
119 20
25 9.7
25/9
18/18
1.8 1.2
COHb ≥4 gdl
(n = 64)
COHb ≤3 gdl
(n = 36)
1
62
113 20
22 7.8
49/17
38/26
6.4 2.1
Results presented as numbers or median and range. Only COHb differed significantly (P < 0.001).
PACU
Postoperative (1 h)
Postoperative (2 h)
Postoperative (4 h)
Postoperative (6 h)
Postoperative (12 h)
Postoperative (24 h)
Day 7
1
2 (1–3)
2 (2–2)
2 (2–2)
2 (2–2)
2 (2–2)
2 (1–2)
2 (1–2)
0 (0–2)
COHb ≥4 gdl
(n = 64)
1
P
3 (2–4)
2 (2–3)
2 (2–2)
2 (2–2)
2 (2–2)
2 (2–2)
2 (1–2)
1 (0–2)
0.020
0.026
0.820
0.195
0.707
0.593
0.987
0.137
Results presented as interquartile ranges.
group [8 (24%, P = 0.003)]. Composite complications
were more common in patients in the high-COHb
group in postanesthesia care unit: 14% vs 47%,
P = 0.0001 [odds ratio:7.4 (95% Cl, lower = 2.5upper = 21.7)] (Table 2). The most common complications were coughing (46%) and desaturation (15%)
(Table 3). In only high-COHb group, two patients
needed re-intubation. Pain scores in postanesthesia care
unit and one hour after surgery were statistically significantly lower in the low-exposure group [respectively,
P = 0.020 (95% CI, lower = 1.21-upper = 0.80),
P = 0.026
(95% CI,
lower = 0.03-upper = 0.70)]
(Table 4). Furthermore, total supplemental tramadol
in the PACU, and at the 4th and 24th postoperative
Table 2 Postoperative complications
COHb ≤3 gdl
(n = 36) (%)
PACU
Postoperative 1 h
Postoperative 2 h
Postoperative 4 h
Postoperative 6 h
Postoperative 12 h
Postoperative 24 h
Day 7
1
5 (14)
5 (14)
1 (2)
1 (2.9)
0 (0)
0 (0)
0 (0)
0 (0)
COHb ≥4 gdl
(n = 64) (%)
35 (47)
25 (22)
2 (3)
0 (0)
3 (4.5)
1 (1.5)
1 (1.5)
1 (1.5)
1
P
0.001
0.342
0.980
0.161
0.207
0.471
0.471
0.471
Results presented as numbers (percentile).
Table 3 Total number of each postoperative complications in 24 h
COHb ≤3 gdl
(n = 36)
Persistent Coughing
Desaturation
Postoperative
Nausea-vomiting
Laryngospasm
Bronchospasm
Postoperative bleeding
COHb ≥4 gdl
(n = 64)
7
1
24
9
2
1
1
0
6
5
3
3
Results presented as numbers.
250
1
hours were statistically significantly lower in the
low-exposure group [respectively, (P = 0.011 95%
CI, lower = 0.51-upper = 0.11), (P = 0.012 95% CI,
lower = 4.16-upper =
0.61), (P = 0.008 95% CI,
lower = 4.32-upper = 0.80)] (Table 5).
Total blood loss was also similar in the high and lowexposure groups: 22 ml vs 25 ml (P = 0.75). Only one
child needed reoperation in high-COHb group because
of secondary hemorrhage.
Discussion
Generally, COHb concentrations up to 1% are accepted
as safe in children (25). In our patients, the mean COHb
concentration was 5% in children having elective tonsillectomies. This concentration is similar to the 5.9%
reported by Yee et al. in children exposed to secondhand smoke (26).
A number of pollutants commonly found indoor
impair respiratory defenses including ciliary function
(27). Larson and Konig reviewed six studies of exposure
to biomass pollution in school-aged children in the United States, and found that exposure was associated with
chronic respiratory symptoms, worsened lung function,
and increased hospital visits (28). A study conducted
near where ours was found in a group of 617 9–12-yearold children that those in homes in which coal stoves
were used coughed more than those living homes in
which kerosene, oil, or electricity was used (27).
1
Table 5 Postoperative analgesic consumption
COHb ≤3 gdl
(n = 36)
PACU (0 h)
Postoperative (1 h)
Cumulative (4 h)
Cumulative (24 h)
1
0 (0–2.25)
0 (0–4.75)
3.5 (0–8)
3.5 (0–8)
COHb ≥4 gdl
(n = 64)
4 (0–5)
0 (0–4.75)
6 (5–9)
6 (5–9)
1
P
0.011
0.943
0.012
0.008
Results presented as interquartile ranges.
© 2014 John Wiley & Sons Ltd
Pediatric Anesthesia 25 (2015) 247–252
O. Koyuncu et al.
Carboxyhemoglobin and perioperative complications in children
CO exposure is also a risk factor for postoperative
complications in infants and children. Lakshmipathy
et al. concluded that the risk of developing postoperative
laryngospasm is an order-of-magnitude great in children
exposed to second-hand smoke (15). Skolnick et al. and
Drowngowski et al. noted that laryngospasm and severe
coughing in the postanesthesia care unit were more common in children exposed to second-hand smoke (16,29).
There is possibility that there are confounding variables
known or unknown that may have influenced the
outcome and that the CO is an association and not causation. For example, CO may be a marker of socioeconomic status that can affect certain outcomes.
We observed that pain and analgesic requirements
were increased in the high-CO patients, especially in the
initial postoperative period. This result is consistent with
Gilbert et al. who demonstrated that long-term exposure to CO augments pain perception (30). Akmal et al.
described the association between smoking and lowback pain via anoxia because of COHb in the blood
(31). Rahman et al. suggested a different mechanism,
explaining that smoking introduces a variety of toxic
substances (e.g., carbon monoxide) that may damage
the interior lining of blood vessels, thus decreasing their
capacity to carry oxygen, leading to tissue starvation,
degeneration, and death (32). Furthermore. carbon
monoxide has been found to play a role in regulation of
nociception by the activation of CGMP-PKG signaling
pathway (33,34). There was an obvious correlation
between COHb and pain ratings especially in early postoperative period in our study. This mechanisms support
our secondary hypothesis that patients with high-CO
concentrations have more pain; our results support the
hypothesis, as analgesic consumption was greater in
high-COHb patients. Although, overall pain scores are
low in both groups which may be related to surgical
technique, making it difficult to interpret.
We relied on children’s parents and caregivers to
identify and quantify second-hand smoke exposure.
Although the related questions were included in a validated questionnaire, it remains possible that parents
failed to accurately or completely report passive
smoking exposure at home for various reasons, including personal embarrassment. An additional limitation is
that we used a relatively new, noninvasive device to
evaluate carboxyhemoglobin rather than blood concentrations; however, the system is well validated and there
were strong associations between COHb concentrations
identified noninvasively and adverse outcomes. Baker
et al. in their study exposed volunteers to carbon monoxide until COHb level reached 15% and later results
were compared with the laboratory blood measurements, which proved a bias of 1.22% and precision of
2.19% (absolute range of error was 6 to +8%) (19).
Studies in emergency department demonstrated a bias
value of 4.2% (95% CI 2.8% to 5.6%) (22,35).
In summary, children with substantial environmental
CO exposure who were given general anesthesia had
more postoperative complications, more pain, and
needed more analgesics than those with less exposure. A
history of coal stove use and second-hand smoke exposure thus has clinical implications and is worth eliciting
—especially as carboxyhemoglobin concentrations can
now be confirmed noninvasively.
Ethical approval
There is no any necessary ethical approval.
Funding
This study was not associated with any grand funding.
Supported by internal funds only.
Conflict of interest
No conflicts of interest declared.
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Appendix 1: The child’s environmental air quality questionnaire (26).
1 Does your house have an indoor coal-burning stove?
a Yes b No
2 How often do you open open the windows during
winter?
a Can not open them
b 2-3 days per week
c Daily
3 Does anyone in your household smoke?
a Yes b No
a Yes b No
5 Does the father smoke?
a Yes b No
6 Is your child permitted to be present in the same room
or car where smoking occurs?
a Yes b No
7 Is there any smoker caregiver at home?
a Yes b No
4 Does the mother smoke?
252
© 2014 John Wiley & Sons Ltd
Pediatric Anesthesia 25 (2015) 247–252