Table 1.
Clinical studies investigating cerebral lactate and pyruvate in subarachnoid hemorrhage.
| Study Design | Sample Size | Age, y (±SD or Range) * |
Sex | Sample (Method) |
Relevant Results | Ref. |
|---|---|---|---|---|---|---|
| R | 46 | 61.0 ± 10.7 | 18 M 28 F |
CSF (LP and cisternal drain) | Elevated CSF pyruvate concentration is strongly associated with poor grade SAH (WFNS ≥ III). | [16] |
| R | 55 | 55 ± 12 | 15 M 40 F |
ISF (CMD) | Biochemical patterns of mitochondrial dysfunction (LPR > 30) in 29 patients, and cerebral ischemia (LPR > 30 and > 40) in 10 patients, including 6 patients who also demonstrated periods of mitochondrial dysfunction. | [29] |
| R | 249 | 55 ± 11 | 102 M 47 F |
Serum | Elevated admission serum lactate is predictive of mortality (3.5 ± 2.5 mmol/L vs. 2.2 ± 1.6 mmol/L). | [30] |
| R | 105 | 59 ± 13 | 34 M 71 F |
Serum | Early (24 h from admission), serum lactate elevation > 2.2 mmol/L (mean of 2.91 mmol/L) did not independently predict patient mortality and discharge (adjusted odds for Hunt and Hess scale, GCS, age and DCI). | [31] |
| P | 20 | 60 (51–64) |
2 M 18 F |
ISF (CMD) | Elevated lactate levels and high LPR (51 ± 36) is correlated with delayed cerebral hypoperfusion (< 32.5 mL/100 g/min) in comatose patients with SAH. | [35] |
| P | 18 | 52 ± 10.7 | 8 M 10 F |
ISF (CMD) | Early (day 3) interstitial lactate levels are elevated in patients with bacterial pneumonia (median, 6.82 mmol/L) compared to those without pneumonia (median, 2.90 mmol/L). | [36] |
| R | 285 | 55 (47–65) |
96 M 189 F |
Serum | Elevated serum lactate levels (≥ 2.1 mmol/L) in first 24 h after SAH are associated with increased risk of DCI and poor outcomes (mRS of 4–6 at 3 months). | [40] |
| R | 145 | 62 ± 16.3 | 44 M 101 F |
Serum | Serum lactate of > 1.1 mmol/L after 48 h of admission is the most accurate predictor of unfavorable neurological outcomes in terms of mRS at discharge. | [41] |
| R | 33 | 61 (26–77) |
11 M 22 F |
CSF (EVD) | No association between elevated CSF lactate > 2.1 mmol/L (at 0–240 h post SAH measurement) and impaired circulation and clinical outcomes. However age (≥ 61 years) and coiling for treatment are significantly correlated with elevated lactate levels. | [42] |
| P | 20 | 60 (32–83) |
9 M 11 F |
CSF (EVD) | CSF lactate in the first 12 days after SAH and an increased LPR on days 5–7 correlated with onset of cerebral vasospasm. | [44] |
| R | 51 | 55 (44–64) |
18 M 33F |
CSF (EVD) | Elevated CSF lactate level (median, 3.2 mmol/L) within 10 days post-SAH correlates with intraventricular hemorrhage and unfavorable outcomes at discharge. | [45] |
| P | 15 | N/A | N/A | ISF (CMD) | Interstitial LPR > 30 is associated with decreased cerebral perfusion, but not with increased ICP of greater than 20 mmHg. | [50] |
| R | 21 | 48 ± 15.9 | 14 M 7 F |
ISF (CMD) | Elevated LPR (50.01 ± 24.79) correlates with increased mortality. Survivors had elevated lactate values (8.52 mmol/L vs. 5.89 mmol/L) compared to non survivors. | [51] |
| R | 30 | 58.9 (28–84) |
5 M 25 F |
ISF (CMD) | Low CBF (< 28 mL/100 g/min), elevated ISF lactate (4.8 ± 2.2 mmol/L), and elevated LPR (32 ± 16) are early warning signs (day 0–3) of DCI before any clinical symptoms appear. | [52] |
| R | 30 | 58.9 (28–84) |
5 M 25 F |
ISF (CMD) | Blood flow measurements and CMD sample monitoring on days 0–3 after onset of SAH showed elevated lactate levels 3.9 ± 2 mmol/L and low regional CBF in territory of the impending ischemia. | [53] |
| P | 19 | 55 (46–73) | 6 M 13 F |
ISF (CMD) | Interstitial pyruvate levels vary with level of consciousness. Between 84 and 132 h after SAH, conscious SAH individuals had normal levels (159–196 µM) but in unconscious SAH patients, pyruvate levels remained low (102–131 µM). | [54] |
| R | 28 | 55.4 | 13 M 15 F |
CSF (intrathecal and intraventricular) | Patients with modified Fisher grades 3 and 4 have elevated intrathecal CSF lactate (> 5.5 mmol/L) on day 7 post SAH and is predictive of poor neurological outcomes and hydrocephalus requiring a shunt. | [55] |
| R | 140 | 48 (47.3–65.5) (patients who developed NPE only) | 48 M 92 F |
Serum | Increase serum lactate levels (54.0 mg/dl), within one hour after SAH are associated with early onset of neurogenic pulmonary edema (NPE). | [56] |
| P | 10 | 52.2 ± 5.0 | 7 M 3 W |
ISF (CMD) | 10 fold increase in lactate levels (baseline levels 100–200 µmol/L) along with increase in excitatory amino acids in SAH showed correlation with poor outcomes at the 3 months (GOS 1 to 3). | [33] |
| P | 22 | 56 (47–68) | 7 M 15 F |
ISF (CMD) | High CMD tau protein was positively correlated with elevated levels of lactate (> 4 mmol/L) and also positively correlated with pyruvate, LPR, and poor functional outcome (mRS ≥ 4) 12 months after SAH after adjusting for disease severity and age. | [39] |
* Age mentioned either in standard deviation (SD) or range. Abbreviations: R, retrospective; P, prospective; y, year; SD, standard deviation; M, male; F, female; SAH, subarachnoid hemorrhage; CMD, cerebral microdialysis; ISF, interstitial fluid; LP, lumbar puncture; GOS, Glasgow coma scale; LPR, lactate-pyruvate ratio; EVD, external ventricular drain; DCI, delayed cerebral ischemia; mRS, modified Rankin Score; CSF, cerebrospinal fluid; GCS, Glasgow coma scale; ICP, intracranial pressure; PCT, perfusion computed tomography; CBF, cerebral blood flow; NPE, neurogenic pulmonary edema; N/A, not available.