Table 2.
Studies investigating predictive value of single or serial blood lactate assessment.
| Author, year, reference | Study design, study quality* | N | Patient characteristics | Lactate characteristics | Outcome measure | Cut off [mM] |
Main findings |
|---|---|---|---|---|---|---|---|
| Shapiro et al., 2005 [2] | Prospective, observational Moderate Acceptable external validity. Acceptable internal validity. Sample size of uncertain adequacy. |
1278 | ED patients with infection-related diagnosis (≥ 18 years). |
Venous lactate at admission to ED. | 3-day and 28-day in-hospital mortality. | 0-2.5; 2.5-4.0; > 4.0 | Mortality rate increased with lactate levels: 0-2.5 mM: 4.9%; 2.5-4.0 mM: 9%; > 4.0 mM: 28%. Area under ROC curve for 3-day mortality was 0.80; for 28-day mortality it was 0.67. For 28-day mortality lactate between 2.5-4.0 mM had sens. 59% and spec. 71%. Lactate > 4.0 mM had sens. 36% and spec. 92%. For 3-day mortality lactate between 2.5-4.0 mM had sens. 76% and spec. 71%. Lactate > 4.0 mM had sens. 55% and spec. 91%. |
| Callaway et al., 2009 [3] | Retrospective Moderate Acceptable external validity. Acceptable internal validity. Sample size of uncertain adequacy. |
588 | Normotensive blunt trauma patients (≥ 65 years). |
Venous lactate at admission to ED. | In-hospital mortality. | 2.5 | Compared to patients with admission lactate < 2.5 mM, lactate > 4.0 mM had OR 4.2 (2.4-7.5) for death. Area under ROC curve was 0.60. |
| Howell et al., 2007 [4] | Prospective, observational Moderate Acceptable external validity. Good internal validity. Sample size of uncertain adequacy. |
1287 | ED patients with infection-related diagnosis. | Venous lactate at admission to ED. | 28-day in-hospital mortality. | 2.5-4.0; > 4.0 | Admission lactate predicted 28-day mortality independently of blood pressure (p < 0.0001). Compared to lactate < 2.5 mM, lactate between 2.5-4.0 mM had OR 2.2 (1.1-4.2). Lactate > 4.0 mM had OR 7.1 (3.6-13.9). Area under ROC curve was 0.87. |
| Khosravani et al., 2009 [11] | Retrospective Moderate Acceptable external validity. Acceptable internal validity. Sample size of uncertain adequacy. |
9036 | Intensive care patients, unspecified (≥ 18 years). |
Arterial or venous lactate at admission to ICU. | ICU mortality. | 2.0 | Lactate was an independent predictor of mortality: 2-5 mM: OR 1.94 (1.62-2.32); 5-10 mM: OR 3.38 (2.64-4.33); 10-15 mM: OR 4.41 (2.99-6.5); 15-20 mM: OR 7.58 (3.93-14.6); 20-max: OR 10.89 (4.85-24.48). All compared to control group with lactate < 2 mM |
| Nichol et al., 2010 [12] | Retrospective Moderate Acceptable external validity. Good internal validity. Sample size of uncertain adequacy. |
7155 | Intensive care patients, unspecified. | Arterial lactate at admission to ICU. Serial: interval unspecified. |
In-hospital mortality. | 2.0 | Compared to lactate < 0.75 mM, admission lactate > 2.0 mM had OR for mortality at 2.1 (1.3-3.5, p = 0.01). Sustained lactate between 0.75-1.0 mM had OR = 2.0 (p < 0.0001). Sustained lactate > 2.0 mM had OR = 3.7 (1.9-7.0, p < 0.0001). |
| Smith et al., 2001[13] | Prospective, observational Moderate Acceptable external validity. Acceptable internal validity. Sample size of uncertain adequacy. |
148 | Intensive care patients, unspecified. | Arterial lactate at admission to ICU. Serial: 24 hours later. |
28-day in-hospital mortality. | 1.5 | Admission lactate > 1.5 mM was associated with 28-day mortality (p < 0.0001). Area under ROC curve = 0.78. Patients with lactate > 1.0 mM at 24 hours have significantly higher mortality (p = 0.0001). |
| Suistomaa et al., 2000 [14] | Prospective, observational Moderate Acceptable external validity. Acceptable internal validity. Sample size of uncertain adequacy. |
98 | Intensive care patients, unspecified. | Arterial lactate at admission to ICU. Serial: every 2 hours the first 24 hours. |
In-hospital mortality. | 2.0 | Median peak lactate for non-survivors was 5.3 mM (IQR, 1.9-7.5) vs. 1.9 mM (IQR, 1.3-2.9) for survivors, p = 0.003. Hyperlactatemia at admission to ICU was associated with higher mortality than hyperlactatemia that developed after admission (29.0% vs. 5.9%, p = 0.003). Persistent hyperlactatemia (> 6 hours) was associated with higher mortality than transient hyperlactatemia (36.8% vs. 0%, p = 0.008). |
| Hatherill et al., 2000 [15] | Prospective, observational Low Acceptable external validity. Uncertain internal validity. Probably underpowered study. |
50 | Children at ICU with shock, and initial hyperlactatemia. | Arterial lactate at admission to ICU. Serial: at 24 hours, and additionally at unspecified intervals. |
ICU mortality. | 2.0 | The area under the ROC curve for all values of lactate > 2 mM on admission was 0.59. Persistent hyperlactataemia > 2 mM after 24 hours was associated with 93% mortality, as compared to 30% in those children whose lactate level had normalised. Persistent hyperlactataemia at 24 hours identified mortality with a likelihood ratio of 7, sens. 78%, and spec. 89%. The area under the ROC curve for lactate > 2 mM at 24 h after admission was 0.86. |
| Cerovic et al., 2003 [16] | Prospective, observational Low Acceptable external validity. Good internal validity. Probably underpowered study. |
94 | Seriously injured patients defined as ISS ≥ 16 who survived ≥ 12 hours. | Arterial lactate at admission to ICU. Serial: every 12 hours during the first 48 hours after admission. |
In-hospital mortality. | 2.0 | Admission lactate was not a significant predictor for mortality. Survivors exhibited a progressive decline in lactate levels, while lactate in the non-survivors remained broadly unchanged from the 12th hour after the first sampling. |
| del Portal et al., 2010 [17] | Retrospective Moderate Acceptable external validity. Good internal validity. Sample size of uncertain adequacy. |
1442 | ED patients (≥ 65 years). |
Lactate at admission to ED. | 30-day and 60-day in-hospital mortality. | 2.0 | Admission lactate were linearly associated with mortality (RR = 1.9 to 3.9) depending on lactate levels (p < 0.01). |
| Jansen et al., 2008 [18] | Prospective, observational Moderate Acceptable external validity. Acceptable internal validity. Sample size of uncertain adequacy. |
124 | Patients who required urgent ambulance dispatching with systolic blood pressure < 100 mmHg, or respiration rate < 10, or > 29, or GCS < 14. | Pre-hospital venous or capillary lactate arrival on the site of injury and at admission to the hospital. | In-hospital mortality. | 3.5 | Mortality was significantly higher in patients with lactate ≥ 3.5 mM at the site of injury (41% vs. 12%; p < 0.001) or at admission to the hospital (47% vs.15%; p < 0.001). Lactate, on average, increased 0.1 mM in non-survivors, whereas in survivors, it decreased 0.6 mM (p = 0.044) Pre-hospital lactate had better prognostic value than vital signs alone. |
| Kaplan et al., 2004 [19] | Retrospective Moderate Acceptable external validity. Acceptable internal validity. Sample size of uncertain adequacy. |
282 | Trauma patients with vascular injury (torso or extremity). | Arterial lactate at admission to trauma center. | 28-day in-hospital mortality. | Admission lactate could discriminate survivors from non-survivors (3.6 mM vs. 11.1 mM, p < 0.001). | |
| Pal et al., 2006 [20] | Retrospective Moderate Acceptable external validity. Acceptable internal validity. Sample size of uncertain adequacy. |
5995 | Trauma patients, unspecified. | Arterial lactate at admission to trauma center. | In-hospital mortality. | 2.0 | Survivors had 3.0 mM, and non-survivors had 5.2 mM (p < 0.0001). Sens. and spec. of an elevated lactate was 85% and 38%, respectively. Area under ROC curve was 0.72. PPV was 4%. |
| Vandromme et al., 2010 [21] | Retrospective Moderate Acceptable external validity. Acceptable internal validity. Sample size of uncertain adequacy. |
2413 | Trauma patients with systolic blood pressure between 90 and 110 mmHg. | Capillary or venous lactate at admission to hospital. | Need for ≥ 6 units packed red blood cells within 24 hours. In-hospital mortality. | 2.5 | Admission lactate was a better predictor for mortality and need for blood transfusion than systolic blood pressure (p < 0.0001). Lactate had area under ROC curve = 0.76 and systolic blood pressure had area under ROC curve = 0.61, p < 0.0001. |
| Arnold et al., 2009 [22] | Retrospective Low Acceptable external validity. Good internal validity. Probably underpowered study. |
166 | ED patients diagnosed with severe sepsis. (> 17 years) |
Venous lactate at admission to ED. Serial: interval unspecified. |
In-hospital mortality | 4.0 | The mean initial lactate for survivors was 4.3 mM (SD = 2.6), while non-survivors had 4.7 mM (SD = 2.8), p = 0.41. The mean serial lactate for survivors was 2.2 mM (SD = 1.6), while non-survivors had 3.6 mM (SD = 2.8), p < 0.001. |
| Guyette et al., 2011 [23] | Retrospective Moderate Acceptable external validity. Good internal validity. Sample size of uncertain adequacy. |
1168 | Trauma patients transported by air. (≥ 18 years) |
Pre-hospital venous or capillary lactate was measured | In-hospital mortality | 2.0 | Pre-hospital lactate was median 3.8 mM (IQR, 2.8-6.1) in those who died and median 2.3 mM (IQR, 1.3-3.4) in those who survived to discharge, p < 0.0001. |
| Trzeciak et al. 2007 [24] | Prospective, observational Low Acceptable external validity. Uncertain internal validity. Sample size of uncertain adequacy. |
1177 | ED patients with diagnosis of sepsis or infection. (> 18 years). |
Venous lactate at admission to ED. | In-hospital mortality and death within 3 days from measurement | 4.0 | Compared to baseline 0.0-2.0 mM, patients with lactate ≥ 4.0 mM had OR 6.1(3.7-10.5) for dying within 3 days from lactate measurement. Sens. 35%. Spec. 92%. Area under ROC curve 0.63. Equivalently lactate ≥ 4.0 mM had OR 3.0(2.0-4.6) for in-hospital death. Sens. 19%. Spec. 93%. Area under ROC curve was 0.56. |
| Kaplan et al., 2008 [25] | Retrospective Low Acceptable external validity. Good internal validity. Probably underpowered study. |
78 | Patients with blunt, or penetrating trauma requiring intensive care | Arterial lactate at admission to ED. | 28-day in-hospital mortality. | 2.2 | Admission lactate could not discriminate survivors from non-survivors (2.3 mM vs. 2.9 m, p = 0.24). Area under ROC curve was 0.6. |
| Van Beest et al., 2009 [27] | Prospective, observational Moderate Acceptable external validity. Acceptable internal validity. Sample size of uncertain adequacy. |
135 | Patients with at least 2 symptoms of shock. (≥ 18 years) |
Pre-hospital capillary or venous lactate. | Length of stay, and in-hospital mortality. | 4.0 | Hyperlactamic patients had significantly higher mortality (12.2% vs. 44.3%, p = 0.002), longer LOS at ICU (p = 0.03), and LOS in hospital (p = 0.04). Area under ROC curve was 0.775. Lactate > 3.2 mM was the optimal cut off with sens. 75% and spec. 72%. |
| Nguyen et al., 2004 [28] | Prospective, observational Moderate Acceptable external validity. Good internal validity. Sample size of uncertain adequacy. |
111 | Patients with severe sepsis or septic shock. (> 18 years). |
Arterial lactate at admission to ED. Serial: at 6 hours. |
60-day in-hospital mortality. | ** Lactate clearance less than 10% in 6 hours was associated with a higher 60-day mortality, than lactate clearance more than 10% (p = 0.007). Sens. 44.7% and spec. 84.4%. |
|
| Claridge et al., 2000 [29] | Prospective, observational Moderate Acceptable external validity. Good internal validity. Sample size of uncertain adequacy. |
381 | Trauma patients requiring intensive care. | Lactate at admission to ED. Serial: every 4-6 hours. |
In-hospital mortality. | 2.4 | ** Patients with sustained hyperlactatemia (> 12 hours) had higher risk of infection (pneumonia etc.) than controls (69.8% vs. 40%, p < 0.001). The mortality rate for patients who developed infection was 7.9% vs. 1.9% (p < 0.05). |
| Jansen et al., 2009 [30] | Prospective, observational Low Acceptable external validity. Good internal validity. Probably underpowered study. |
394 | Intensive care patients with sepsis, hemorrhage, or other conditions of low oxygen transport. | Arterial lactate at admission to ICU. Serial: 12 and 24 hours after admission. |
In-hospital mortality. | 2.5 | ** Reduction of lactate within 24 hours was associated with significantly lower mortality in the septic group (p = 0.003), but not in the other groups, (p = 0.42). |
| Kliegel et al., 2004 [31] | Retrospective Moderate Acceptable external validity. Acceptable internal validity. Sample size of uncertain adequacy. |
394 | Patients resuscitated after cardiac arrest who survived > 48 hours. | Arterial lactate. First sample at admission to ED. Serial: every 4-8 hours. |
In- hospital mortality. | 2.0 | On admission survivors had 7.8 mM (IQR, 5.4-10.8) and non-survivors had 9 mM (IQR, 6.5-11.9), p < 0.01. Lactate > 2 mM after 48 hours predicted mortality with a spec. of 86%, and poor neurologic outcome with a spec. of 87%. Sens. for both were 31%. |
| Jansen et al., 2010 [32] | Randomised, controlled trial High Acceptable external validity. Good internal validity. Premeditated and sufficient study size. |
348 | Intensive care patients, unspecified. (≥ 18 years). |
Arterial lactate at admission to ICU. (venous and capillary lactate was also allowed). Serial: every 2 hours. |
In-hospital mortality. | 3.0 | ** Hazard ratio in the intervention group was 0.61 (0.43-0.87, p = 0.006). Reduction of lactate below 2.0 mM was not associated with better outcome. |
| Jones et al., 2010 [33] | Randomised, controlled trial High Acceptable external validity. Good internal validity. Premeditated and sufficient study size. |
300 | Patients with severe sepsis and hypoperfusion or septic shock. (≥ 17 years). |
Venous lactate at admission to ICU. Serial: every hour. |
In-hospital mortality. | 2.0 | ** No difference in mortality was observed in patients treated by a protocol aiming at normalizing blood lactate compared to normalizing SvO2. |
| Blow et al., 1999 [43] | Prospective, intervention Low Acceptable external validity. Uncertain internal validity. Probably underpowered study. |
79 | Hemo-dynamic stable trauma patients with ISS ≥ 20 and survival > 24 hours. | Lactate at admission to trauma centre. Serial: interval unspecified. |
In-hospital mortality. | 2.5 | ** Persistent hyperlactatemia after 24 hours was associated with increased mortality (p < 0.05). |
| Lee et al., 2008 [44] | Prospective, observational Low Acceptable external validity. Good internal validity. Probably underpowered study. |
126 | Patients with severe sepsis, or septic shock. (≥ 20 years). |
Arterial lactate at admission to ED. Serial: 4 hours later. |
In-hospital mortality. | 2.0 | ** No significant difference in mortality was found between patients with elevated lactate compared to normal lactate, as long as pH was within normal limits. |
Numbers in brackets are 95% confidence interval unless specified otherwise. *quality rated by using methods validated for internal validity, precision, and applicability (external validity) [9]. **Predictive value of admission lactate in relation to mortality not commented. ED = emergency department; ROC = receiver operating characteristic; sens. = sensitivity; spec. = specificity; OR = odds ratio; ICU = intensive care unit; IQR = interquartile range; ISS = injury severity score; RR = relative risk; GCS = Glascow coma scale; PPV = positive predictive value; SD = standard deviation; LOS = length of stay; SvO2 = central venous oxygen saturation.