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Three Part Question

In [adult patients with CO poisoning] does [venous/arterial lactate] predict [need for treatment/observation and morbidity]

Clinical Scenario

A 50-year-old male presents to the Emergency Department with suspected carbon monoxide (CO) poisoning following an attempted suicide. He is haemodynamically stable; but is noted to have mild confusion and you are unsure if he requires admission for further monitoring or hyperbaric oxygen (HBO) therapy.

Search Strategy

Medline (1946-2017), Embase (1974-2017) and Cochrane Databases (2007-2017). Search terms included [(lactate).ti,ab AND (initial.ti,ab OR admission.ti,ab OR emergency.ti,ab) AND (carbon monoxide).ti,ab]

Search Outcome

7 papers were found. Articles were reviewed for relevance; 2 were not relevant to the research question and 1 was not available in full text. The remaining 4 papers were relevant and of sufficient quality and are presented below.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
NÖ Do?an et al. 2015 Turkey	74 adults presenting to a single centre Emergency Department over a one-year period with CO intoxication Venous lactate measured.	Retrospective cross-sectional study	Venous Lactate (mmol/L)	Treated with normobaric oxygen therapy 1.0 (0.9-1.7) vs HBO 2.3 (1.7-3.1), p<0.001	Relatively small sample size. Single centre and retrospective study. Small number of patients with elevated lactate.
			Area under ROC curve (AUC) for accuracy predicting HBO treatment for plasma lactate concentration	0.838 (95% CI 0.743-0.933)
			Predicting need for HBO treatment Venous lactate of 1mmol/lL: Negative predictive value	96.3%
			Predicting need for HBO treatment: Venous lactate of 1.85 mmol/L Sensitivity	70.8%
			Predicting need for HBO treatment: Venous lactate of 1.85 mmol/L Specificity	78%
			Predicting need for HBO treatment : Altered mental status	More common in lactate >2.1 mmol/L (73.7% vs. 10.9%, p<0.001)
Cervellin G et al. 2014 Italy	38 adult patients with CO poisoning admitted (median age 37) to a single centre Emergency Department between 2012 and 2013. Arterial lactate measured.	Retrospective review	Predictor of hospital admission	No admission, lactate 1.2 (IQ 1.0-1.6) vs. admission 1.8 (IQ 1.4-2.0) (p<0.001)	Retrospective study, with little discussion of the study limitations. Limited generalisability due to small sample size and single centre study.
			Lactate AUC for predicting hospital admission	0.85 (95% CI, 0.72–0.97; p<0.001)
			Predictor of need for HBO treatment	No HBO, lactate 1.1 (IQ 1.0-1.6) vs. HBO treatment 1.5 (IQ 1.3-1.9) (p=0.003)
			Lactate AUC for predicting HBO treatment	0.54 (95% CI, 0.31–0.78; p=0.366)
			Lactate >1.2mmol/L for predicting need for hospital admission: Sensitivity	1.00
			Lactate >1.2mmol/L for predicting need for hospital admission: Specificity	0.57
Moon JM et al. 2010 South Korea	80 adult patients with CO poisoning reviewed retrospectively. Single centre study with data obtained from December 2005-May 2010. Venous or arterial not defined.	Retrospective cohort study	Altered Mental State on admission	High lactate (>2.1mmol/L) n=38 (67.9%) vs. normal lactate (0.7-2.1 mmol/L) n=10 (41.7%); p=0.028	Single centre and relatively small sample size. Cyanide co-intoxication could not be excluded. Participants excluded if source could not be identified or if inhaled smoke in a confined space therefore limiting applicability. Delayed neurotoxicity days/weeks after exposure not measured.
			Univariate analysis	Elevated lactate associated with poorer short term outcome (odds ratio=1.347, 95% CI 1.103-1.645; p=0.003)
			Multivariate logistic regression: Medical complications defined as neurological deficit at discharge, respiratory failure, hypotension and myocardial injury.	Lactate (mmol/L) was found to be an independent factor associated with medical complications (odds ratio=1.736, 95% CI 1.406-2.883; p=0.033)
Inoue S, Saito T, Tsuji T, Tamura K, Ohama S, Morita S et al. 2008 Japan	3 adult patients with CO poisoning following group suicide attempt. Single centre. Serum lactate measured.	Case report	Raised lactate on admission to ED in all 3 patients. All patients treated with HBO.	Age, time of onset of poisoning and treatment administered were almost identical. Therefore authors concluded that initial blood lactate level might be related to respective outcomes. All patients had initial GCS of 6, received initial 2 hours of HBO and then 2 hours a day for 10 days prior to discharge. Patient 1, initial lactate 75.1mg/dL (4.17mmol/L), remained comatose despite treatment, and died on day 31 due to central diabetes insipidus. Patient 2, initial lactate 41.9mg/dL (2.32mmol/L) was discharged after treatment. Re-presented with delayed encephalopathy on day 45. Patient 3, initial lactate 26.3mg/dL (1.46mmol/L) discharged after treatment with no delayed neuropsychiatric sequelae at 1 year follow up.	Single Centre. Small sample size. Correlation between Lactate and outcomes is speculative.

Comment(s)

This search revealed three retrospective cohort studies and one case report. Differing methodology including lactate sampling and clinical outcomes were reported, limiting comparability between studies. In the carbon monoxide poisoned population, elevated lactate levels appears to correlate with an increase in altered mental state at initial presentation, as well as predicting the need for hospital admission and HBO treatment requirement. However the narrow ranges of elevation, relatively small patient numbers and additional factors that influence lactate measurements needs to be taken into consideration in determining its use. In addition, the correlation of raised lactate in carbon monoxide poisoning to long term sequelae have not been adequately assessed in these studies. Further research is required in this area to determine the role of lactate and its use in predicting patient outcomes in carbon monoxide poisoning. This may require collaboration across multiple centres, which would both increase study size and comparability of findings.

Clinical Bottom Line

Although evidence is limited, it appears that initial lactate measurement may correlate with need for treatment, hospital admission and risk of medical complications in carbon monoxide poisoning. However, given the limitations and the practicality of interpreting lactate based on narrow ranges, no clear conclusion regarding its use to predict patient outcomes in carbon monoxide poisoning can yet be established.

References

1. Do?an N, Savrun A, Levent S, Günayd?n G, Çelik G, Akküçük H, et al. Can initial lactate levels predict the severity of unintentional carbon monoxide poisoning? Human & Experimental Toxicology 2014;34(3):324–9.
2. Cervellin G, Comelli I, Rastelli G, Picanza A, Lippi G Initial blood lactate correlates with carboxyhemoglobin and clinical severity in carbon monoxide poisoned patients Clinical Biochemistry 2014;47(18):298–301.
3. Moon JM, Shin MH, Chun BJ The value of initial lactate in patients with carbon monoxide intoxication: in the emergency department Human & Experimental Toxicology 2010;30(8):836–43.
4. Inoue S, Saito T, Tsuji T, Tamura K, Ohama S, Morita S, et al . Lactate as a prognostic factor in carbon monoxide poisoning: a case report Am J Emerg Med 2008; 26(966) [e1-966.e3].