This project stemmed from interest in two separate, yet connected, areas of paramedic practice, fluid resuscitation and sepsis. Separate investigations into these two areas identifed lactic acid, or lactate, as an area of interest. This review was conducted to identify the key literature on lactate measurement, and the implications for pre-hospital practice.
The research question was formed to be as inclusive as possible after initial investigations revealed lactate measurement has been studied in a range of clinical areas. It was decided to consider the range of possibilities for the use of lactate measurements in the pre-hospital environment. The use of pre-hospital lactate measurement has only recently become possible as technological advances have made the machines portable. Paramedic education has also developed to the point where paramedics can make clinical use of this type of information.
Lactate
Lactate was frst described in the late 18th century by KW Scheele, a Swedish chemist. Lactate can be produced in all bodily tissue but is mainly produced by the skeletal muscles, skin, red blood cells, brain and intestines. Lactate is primarily metabolised in the liver and kidneys, with the average level being less than 2 mmol/l. Hyperlactatemia has classically been associated with anaerobic metabolism due to hypoxia. Recent research has linked elevated lactate levels with other diseases (Okorie and Dellinger, 2011).
Macpherson (1999) describes lactic acid as:
‘Produced in the body during muscular activity, the lactic acid being derived from Article accepted for publication: 14 May 2012 the breakdown of glycogen. Muscle fatigue is associated with an accumulation of lactic acid in the muscle. Recovery follows when enough oxygen gets to the muscle, part of the lactic acid being oxidised and most of it then being built up once more into glycogen.’
Van Beest et al (2009) describe how lactate is a common measure used in sports and exercise to determine anaerobic threshold and intensity levels. In medicine lactate is used as an indicator of ‘tissue hypoxia and disease severity’.
Methods
The initial literature search was conducted using the following search terms: Lactate* AND (paramedic* OR EMS* OR pre-hospital* OR pre-hospital* OR ambulance).
Emergency was considered as a search term but was removed due to the number of results generated focusing on in-hospital emergency department practice. The lack of standard terms for pre-hospital practitioners was a diffculty that was encountered. This resulted in the focus of the search being on lactate measurement with pre-hospital application being used to judge relevance.
The databases used for the initial search were chosen due to availability of access and familiarity of the authors: NHS Databases (AMED, BNI, EMBASE, HMIC, MEDLINE, PsycINFO, CINAHL, HEALTH BUSINESS ELITE), Cochrane Library and Northumbria University Library search facility (NORA).
Results
The initial search using the NHS Databases identifed 362 results, de-publication narrowed this to 157 of which 16 were judged relevant to the initial search. Relevance was judged based on title and abstract by GM. Further searches of the Cochrane Library and NORA revealed no additional literature.
Full text articles were obtained for all 16 articles which were then appraised and reviewed by all three authors. The articles reviewed were classifed as having either a high, medium or low relevance to the study question and the implications for practice were discussed. At this time some potential gaps in the literature were identifed. The papers identifed as having a high level of relevance were used to form the basis of this review.
A secondary search of the literature was conducted using the reference lists of the initial articles. This extended search identifed 13 further articles which were used to expand upon the conclusions drawn from the initial appraisal and discussion. Due to the recent nature of the literature identifed it was decided not to extend the literature search further through the use of citation searching.
Review
Three major themes emerged from the examination and discussion of the literature:
Lactate measurement in the pre-hospital setting
A number of studies have demonstrated that lactate can be measured in the pre-hospital environment (Coats et al, 2002; Jansen et al, 2008; Van Beest et al, 2009; Guyette et al, 2011). Prause et al (2001) and Guyette et al (2011) describe how lactate analysis machines are now small, portable, rugged and fast enough to be practical for use outside of a hospital and the costs associated are not prohibitive. Lactate monitors are very similar to the blood glucose monitors in common use on ambulances, which should aid in overcoming any reluctance to use new technology; however one trial in the Netherlands (Van Beest et al, 2009) found only 50 % compliance when ambulance crews were measuring lactate.
Barriers to compliance included reluctance to repeat measurements, lack of experience handling the machine and strict inclusion criteria. The training requirements for the introduction of this new technology appear achievable. Some studies identifed that short training sessions of one to two hours among other training delivery methods were effective (Van Beest et al, 2009; Erwin et al, 2011). Author correspondence indicates that currently only one ambulance service in the UK is trialling pre-hospital lactate analysis.
Pearse (2009) questioned the variation in lactate levels between venous blood used in portable analysers and the central/arterial blood levels used in hospital. One comparison study (Karon et al, 2007) raised concerns over differences reported at high (>6 mmol/l) levels and advised caution when comparing values taken using differing methods. This point has been addressed and recent papers (Lavery et al, 2000; Van Beest et al, 2009; Creed, 2011) concluded that there may be some variation in the accuracy of the levels reported but the differences are not signifcant.
The technology is available to allow lactate to be measured in the pre-hospital environment.
Paramedics use similar monitors as part of their practice and any barriers to the use of lactate analysers could be overcome with training and organisational support. Comparison of pre-hospital and in-hospital values should be conducted to ensure there are no signifcant differences.
Lactate relevance to conditions encountered in the pre-hospital setting
The majority of literature on pre-hospital lactate measurement has focused on hypovolemic or septic shock. One small hospital-based study (Krishna et al, 2009), including a range of trauma and septic patients, found that serial lactate measurements can be linked to patient mortality. An early study (Coats et al, 2002) using London Helicopter Emergency Medical Service (HEMS) found a moderate correlation between early elevations in lactate and injury severity. This study included a small sample (n=22) who were compensating for their injuries and therefore classifed as ‘diffcult to triage’.
Jansen et al (2008) tested pre-hospital lactate in a patient population classifed as needing ‘urgent ambulance dispatch’ and it was found that lactate was a better indicator of mortality than other traditional pre-hospital observations. A study by Guyette et al (2011) demonstrated the use of pre-hospital lactate to improve predictions of death, the need for surgery and multi-organ failure using a large sample of trauma patients (n=1 168) who were transported by helicopter.
Vandromme et al (2010) showed that increased lactate is more accurate at predicting patients requiring large volumes of transfused blood as opposed to systolic blood pressure (SBP). A study on patients with traumatic inferior vena cava injuries (Rosengart et al, 1999) showed a clear correlation between elevated lactate levels and increased morbidity. Lactate is not affected by alcohol or drugs which makes it a useful test in the pre-hospital environment for trauma patients due to the fact that alcohol is associated with increased risk of trauma (Dunne et al, 2005; Vandromme et al, 2010).
Recent work by Mikkelsen et al (2009) and Seymour et al (2010) show that sepsis is a condition on the increase with high fnancial implications for the health services. Sepsis is a condition where early identifcation and treatment can have a positive impact on patient outcomes and where pre-hospital care can be linked to improved outcomes by shortening the time to IV fuids and antibiotics (Goyal et al, 2010; Seymour et al, 2010; Studnek et al, 2010; Band et al, 2011).
Studnek et al (2010) describe how pre-hospital lactate could be incorporated into a range of measures designed to aid ambulance staff in rapid, accurate identifcation of sepsis. Paramedics have been shown to be able to diagnose sepsis, with the aid of pre-hospital lactate, but were unable to accurately gauge the severity of the condition (Erwin et al, 2011).
Mikkelsen et al (2009) showed that lactate has been associated with mortality in a large sample (n=830) of septic patients, independent of organ dysfunction or shock. The utility of individual measurements and trends of lactate levels has been demonstrated by Bakker and Jansen (2007) in a sepsis case–study–based editorial piece. Hand held lactate analysers have been shown to reduce the time to results when compared to standard laboratory analysis, which has implications for improving the time to treatment for septic patients (Goyal et al, 2010).
Other uses of pre-hospital lactate have been documented including one study which described the use of lactate as an indicator of patient prognosis in cases of carbon monoxide (CO) poisoning (Moon et al, 2010). A small case report from Japan supported the use of lactate in cases of CO poisoning (Inoue et al, 2008). Paracetamol overdoses can lead to acute liver failure and Bernal et al (2002) showed that lactate has the potential to aid in selection of cases requiring urgent treatment.
High lactate levels have been observed, along with other markers, in hypothermic post–cardiac– arrest patients (Kornberger et al, 1999). The detection of severe acidosis, by the measurement of arterial lactate, in cardiac arrest cases has been described with the possibility of using pre-hospital lactate to guide resuscitation attempts (Prause et al, 2001). A single small study discussed the use of lactate to predict mortality after major burns (defned as burns >15 % total body area) and raised the potential of using lactate as a target for resuscitation (Jeng et al, 2002). Recent research has indicated that pre-hospital lactate can be used in STEMI patients to improve assessment and highlights a connection between lactate and cardiogenic shock (Vermeulen et al, 2010).
The vast majority of studies identifed and included focused exclusively on adults (aged >17 years). One paper from Brazil by Koliski et al (2005) discussed lactate in a small paediatric sample (n=75) and concluded that serial measurements of blood lactate were prognostic of mortality in paediatrics. The recent ILCOR resuscitation guidelines indicate that an optimal set of tests to diagnose paediatric shock should include lactate measurement (Nolan et al, 2010).
Implications for paramedic practice
Lactate measurements may aid paramedics in identifying and assessing the severity of some conditions encountered in the pre-hospital environment. Hypovolemic shock and sepsis are two conditions where there is literature supporting the use of lactate measurements to aid paramedic decision making. Any use of lactate measurement would require a combination of a good understanding of the processes involved in order to judge which readings were signifcant and protocols on which conditions lactate readings were applicable to. A normal lactate level does not rule out an injury but when used in conjunction with other fndings it may aid in the triage or assessment of the extent of occult injuries.
Lactate has been found to outperform other traditional observations such as pulse and blood pressure when predicting mortality
Paramedics using lactate will need an awareness of conditions which may generate abnormal lactate levels. Case studies have described lactic acidosis in patients experiencing seizures and epileptic patients have been excluded from trials on lactate levels due to the lack of sensitivity of hyperlactataemia in post-ictal patients (Lipka and Bulow, 2003; Jansen et al, 2008).
A comprehensive review of the literature around the use of lactate as a biomarker was recently published which concluded that changes in lactate levels over time are independently associated with death in a variety of settings. This review suggested that the use of a lactate level to trigger a treatment protocol and guide early treatment made it a useful biomarker (Okorie and Dellinger, 2011).
Lactate has been found to outperform other traditional observations such as pulse and blood pressure when predicting mortality with the conclusion that pre-hospital lactate can be used to identify seriously ill patients that would not normally be detected (Gunnersen et al, 2009). One study calculated that the addition of arterial lactate to the traditional vital signs used to triage trauma patients increased the sensitivity from 41 % to 76 % for detection of major injuries (Paladino et al, 2008). Additional studies have described the use of lactate to detect occult injuries and improve triage decisions in normotensive patients (Van Beest et al, 2009). This paper included information on fuid administration to promote lactate clearance and improve overall outcome.
The classical signs of septic shock are not evident in large numbers of patients transported by ambulance and classifed as septic, whereas increased lactate was associated with lower SaO2, SBP and GCS. This study also highlighted the variability in pre-hospital treatment of sepsis and identifed that pre-hospital identifcation and treatment require further study (Seymour et al, 2010).
Robson et al (2009) discussed the importance of pre-hospital identifcation of sepsis and the potential for improvements in diagnosis, treatment and patient outcomes. This paper describes how lacate can be added into a pre-hospital screening tool and used as a trigger for treatment pathways. This paper also calls for more research in this area and increasing the importance given to sepsis treatment.
Advanced Trauma Life Support (ATLS) is in widespread use in pre-hospital care and classifes shock into four distinct stages. In ATLS a decreased SBP is not evident until stage 3 shock, but a recent study does not support this association. In this study patients in stage 4 shock, as defned by estimated blood loss >40 %, had a median SBP of 120 mmHg with a lower interquartile range of 98 mmHg. With reference to the treatment of shocked patients the data shows low numbers of patients given fuid, including pre-hospital, but the data is incomplete (Guly et al, 2011).
Vandromme et al (2010) question the use of SBP <90 mmHg as a defnition of hypotension. These observations are supported by a recent study by Guyette et al (2011) that found that ‘Compensated shock is not easily recognisable by prehospital providers.’
Pre-hospital lactate can be used to improve pre-hospital triage, trigger treatment algorithms and inform choice of destination (Jansen et al, 2008; Pearse, 2009; Guyette et al, 2011).
It has been shown that high lactate is associated with increased mortality in normotensive elderly blunt trauma patients, who are a group that are classically under-triaged (Calloway et al, 2009). A study conducted on a large sample (n=2 519) of trauma patients over a nine-year period, suggested that pre-hospital lactate can improve triage decisions and choice of destination as it was a better predictor of the need for blood and patient mortality (Vandromme et al, 2010). The development of bypass protocols incorporating lactate measurement could infuence patient fow to the regional trauma centres being established across the UK, although the potential for over-triage and overwhelming trauma centres has been raised (Vandromme et al, 2010).
Not all of the literature supports the widespread use of lactate measurement in the pre-hospital environment. One large (n=5 995) retrospective study concluded that individual lactate measurements were not prognostic of mortality. This study did fnd use for measuring trends in lactate levels and advocated using these in severely injured patients (Pal et al, 2006).
Pre-hospital lactate has the potential to aid in several areas of paramedic practice. Lactate could be used to aid triage in large incidents for teams such as HART (Hazardous Area Response Team). Lactate could be used to aid in the early detection of trauma that would beneft from being transferred directly to a major trauma centre as opposed to the nearest hospital. Lactate could aid the diagnosis of medical conditions such as sepsis and act as a trigger for an associated treatment package. Sepsis identifcation can be improved through a number of means, such as early warning scores or more accurate thermometers, so lactate is not the only option for improvement but could be considered as part of a package of improvements.
Further research
Further research into this area is needed. There are a number of aspects of this topic that could be explored including:
Study limitations
It is acknowledged that this review may have missed some relevant literature and that the use of additional search engines or citation searching may have identifed further literature. The expansion of the search criteria to include additional methods of searching, such as citation chaining and non-English language papers, would expand the literature base to draw upon and improve the overall results. The fact that a number of articles that were not identifed in the literature search were added due to author awareness shows that improvements could be made in the search methodology.
Conclusion
Lactate has been shown to be prognostic of mortality. Trends in lactate levels can be used to guide and monitor treatment across the whole of the patient's journey from initial injury through to discharge from hospital. Lactate can be measured in the pre-hospital environment by paramedics and this could be used to guide paramedic treatment in certain categories of patients. The authors are confdent that this review of the literature indicates the potential for incorporating pre-hospital lactate into paramedic practice. In the authors' opinion further research is necessary in this area.