**5.2.1 Preoperative**

*The Risk-Adjusted Classification for Congenital Heart Surgery* (RACHS-1) system for mortality risk adjustment has recently been proposed as a universal objective score for adjusting differences in case mix when examining in-hospital death rates after congenital heart surgery, and for predicting the risk involved in specific types of cardiac surgery (Jenkins & Gauvreau, 2002; Jenkins et al., 2002). RACHS-1 assigns congenital heart surgical cases to one of six risk categories based on the presence or absence of specific diagnosis and procedure codes, where category 1 has the lowest risk of death and category 6 has the highest. When the mean lactate level was measured at four time points for each RACHS-1 subgroup, blood lactate levels absolutely correlated with the RACHS-1 subgroups at each of the time points (r2>0.89 for all) (Molina Hazan et al., 2010). In addition, the progression of lactate levels over time differs significantly between patients with different RACHS-1 scores (P = 0.029).

*The patient's age* affects the risk for postoperative hyperlactatemia. Children younger than 1 year of age would be primed with banked red blood cells and have comparatively more banked blood peri-operatively and higher risk for developing postoperative hyperlactatemia and lactic acidosis (Zhou & Liu, 2011). The adult patient's age is not a predictor for hyperlactatemia.

*The electivity/urgency* of the surgery are also influential: the more elective the surgery, the lower the postoperative blood lactate levels are expected (Maillet et al., 2003). Urgent or emergency surgery is usually performed for patients who are hemodynamically unstable, and so the preoperative lactate values might have already been abnormal in some of them.

Non-pre-existing hyperlactatemia during CPB for cardiac operations in *adults* is favored by the preoperative risk profile (high serum creatinine values and active endocarditis) and by prolonged (> 96 minutes) CPB times, in addition to being associated with hyperglycemia (Ranucci et al., 2006). Patients with a blood lactate level of 4.0 mmol/L (36 mg/dL) or higher were older and were more often females. The prevalence of congestive heart failure, left ventricular ejection fraction less than 30%, and arteriosclerosis was significantly higher among the patients with hyperlactatemia (Demers et al., 2000).

#### **5.2.2 Peri-operative**

Hyperlactatemia occurring early after CPB may represent intra-operative or early postoperative tissue oxygen debt, impaired lactate clearance, or both. It may, however, follow CPB despite well-maintained oxygen delivery and a normal perioperative course. The duration of CPB and, especially, the occurrence of hypotension at the start of the bypass period appears to be related to the development of lactic acidosis. Non-pulsatile, hypothermic CPB itself has a potential for impairment of peripheral perfusion and thus of metabolic balance, since it is associated with collapse and sludging in capillary vessels

of CHD despite evidence of good cardiac output. Cardiac arrest or severe hypovolemia triggers anaerobic metabolism and hyperlactatemia, all of which can appear pre-, peri- or postoperatively due to the many cardiac or resuscitation problems found in pediatric

Changes in lactate levels in post-cardiac surgery patients are not homogenous in nature, due to the fact that early hyperlactatemia and late hyperlactatemia differ in both risk profile and

*The Risk-Adjusted Classification for Congenital Heart Surgery* (RACHS-1) system for mortality risk adjustment has recently been proposed as a universal objective score for adjusting differences in case mix when examining in-hospital death rates after congenital heart surgery, and for predicting the risk involved in specific types of cardiac surgery (Jenkins & Gauvreau, 2002; Jenkins et al., 2002). RACHS-1 assigns congenital heart surgical cases to one of six risk categories based on the presence or absence of specific diagnosis and procedure codes, where category 1 has the lowest risk of death and category 6 has the highest. When the mean lactate level was measured at four time points for each RACHS-1 subgroup, blood lactate levels absolutely correlated with the RACHS-1 subgroups at each of the time points (r2>0.89 for all) (Molina Hazan et al., 2010). In addition, the progression of lactate levels over time differs significantly between patients with different RACHS-1

*The patient's age* affects the risk for postoperative hyperlactatemia. Children younger than 1 year of age would be primed with banked red blood cells and have comparatively more banked blood peri-operatively and higher risk for developing postoperative hyperlactatemia and lactic acidosis (Zhou & Liu, 2011). The adult patient's age is not a

*The electivity/urgency* of the surgery are also influential: the more elective the surgery, the lower the postoperative blood lactate levels are expected (Maillet et al., 2003). Urgent or emergency surgery is usually performed for patients who are hemodynamically unstable, and so the preoperative lactate values might have already been abnormal in some of them. Non-pre-existing hyperlactatemia during CPB for cardiac operations in *adults* is favored by the preoperative risk profile (high serum creatinine values and active endocarditis) and by prolonged (> 96 minutes) CPB times, in addition to being associated with hyperglycemia (Ranucci et al., 2006). Patients with a blood lactate level of 4.0 mmol/L (36 mg/dL) or higher were older and were more often females. The prevalence of congestive heart failure, left ventricular ejection fraction less than 30%, and arteriosclerosis was significantly higher

Hyperlactatemia occurring early after CPB may represent intra-operative or early postoperative tissue oxygen debt, impaired lactate clearance, or both. It may, however, follow CPB despite well-maintained oxygen delivery and a normal perioperative course. The duration of CPB and, especially, the occurrence of hypotension at the start of the bypass period appears to be related to the development of lactic acidosis. Non-pulsatile, hypothermic CPB itself has a potential for impairment of peripheral perfusion and thus of metabolic balance, since it is associated with collapse and sludging in capillary vessels

among the patients with hyperlactatemia (Demers et al., 2000).

patients with CHD.

**5.2.1 Preoperative** 

scores (P = 0.029).

**5.2.2 Peri-operative** 

predictor for hyperlactatemia.

physiological rationale (O'Connor & Fraser, 2010).

according to duration of the CPB and to lactate concentration fluctuations (increase after the start of CPB, remaining elevated during CPB, decreasing after CPB, and increasing again after surgery).

Patients with lactate levels of 4.0 mmol/L (36 mg/dL) or higher had significantly longer CPB time and aortic cross-clamping time, and the lowest hemoglobin value recorded during CPB tended to be lower in patients with lactate levels of 4.0 mmol/L (36 mg/dL) or higher (Demers et al., 2000).

Postoperative hyperlactatemia following cardiac surgery was associated with the longest CPB duration and the more frequent intraoperative administration of vasopressors (Maillet et al., 2003). A significant association was found between either duration of CPB or arterial pH and lactate in a retrospective study (Duke et al., 1997). Type A lactic acidosis during CPB appears to be multifactorial.

In a retrospective study where hyperlactatemia was defined as 5 mmol/L (45 mg/dL) or more, CPB duration in the hyperlactatemia group was significantly longer than for the normal lactatemia group in adults undergoing cardiac surgery. Moreover, significant elevations of serum lactate were observed after the start of CPB in the hyperlactatemia group, while other intraoperative variables, including the degree of induced hypothermia, were similar between the two groups (Inoue et al., 2001). In that study, significant correlations between maximal lactate concentration and duration of CPB and aortic crossclamping were observed as well.

Abraham et al. (2010) compared perioperative factors in 26 patients with postoperative hyperlactatemia (lactate greater than 3 mmol/L (27 mg/dL))) to 42 patients with lownormal lactatemia, including bypass time, crossclamp time, mixed venous oxygen levels, peripheral oxygen saturation, pump flow, intraoperative mean arterial blood pressure, lowest intraoperative core temperature, rewarming time, duration of surgery, duration of anesthesia, average intraoperative hemoglobin, intraoperative oxygen content, and intraoperative oxygen delivery. Of all these intra-operative measurements, the authors found the two groups to differ significantly only in pump flow and intra-operative oxygen delivery. The weight-indexed CPB flow rate was an independent predictor of postoperative high lactate (P<.007), and the odds ratio was 7.67 for postoperative hyperlactatemia when it was less than 100 mL/kg/min. Higher mean arterial blood pressure was associated with a reduced risk of high lactate blood levels. An increase of 1 mm Hg, with a fixed CPB flow, resulted with odds ratio for postoperative hyperlactatemia of 0.8343 (P<.009) (Abraham et al., 2010). The nadir temperature, duration of cooling and rewarming, hematocrit during and after CPB, and systemic inflammatory response to CPB were also proposed as being likely predictors for postoperative hyperlactatemia (Abraham et al., 2010; Cheung et al., 2005; Munoz et al., 2000).

An association was found between the duration of extracorporeal circulation and the magnitude of hyperlactatemia developing in the early post-pediatric cardiac operation period in Bakanov et al.'s (2009) work as well.

Finally, massive exogenous D-lactate Ringer's solution infusion during surgery can also cause iatrogenic hyperlactatemia in infants with immature liver function (Zhou & Liu, 2011).

#### **5.2.3 Postoperative**

Metabolic disturbances, such as changes in blood acid-base balance and electrolytic composition, hyperglycemia and hyperlactatemia, are factors that frequently complicate the early postoperative period in patients after cardiac surgery under extracorporeal circulation. Post-cardiac surgery hyperlactatemia is mostly the consequence of excess lactate production, although a reduction of hepatic lactate clearance may contribute to the condition. Early postoperative measurable adverse effects, such as base deficit, maximal anion gap and bicarbonate levels, were significantly different between patients with postoperative hyperlactatemia and patients with low-normal lactatemia in the early postoperative period (i.e., less than 12 hours after admission to the ICU), while postoperative lactate and glucose levels were significantly correlated (Abraham et al., 2010; Chiolero et al., 2000).

Inadequate tissue oxygen delivery because of impaired cardiac output after pediatric cardiac surgery is a relatively common problem which can be expressed in early stages by hyperlactatemia, and one that has been associated with significant morbidity and mortality (Chakravarti et al., 2009).

Elevated lactate concentrations were associated with metabolic acidosis following cardiac surgery. Moreover, postoperative episodes of hypotension, hyperglycemia, and epinephrine, norepinephrine or dobutamine consumption were more frequent in patients with hyperlactatemia following cardiac surgery compared to patients with non-elevated blood lactate levels (Maillet et al., 2003).

Clinical indicators used for diagnosing decreased cardiac output other than hyperlactatemia include a low peripheral temperature/core temperature gradient, long capillary refill time, high pulse and low blood pressure, decreased urine output and base deficit (Bohn, 2011). Most of these indicators do not reflect cardiovascular performance very well (Tibby et al., 1997).

Averaged cerebral and renal rS02 levels of less than 65% as measured by near-infrared spectroscopy (NIRS) predict hyperlactatemia (>3 mmol/L, 27 mg/dL ) in acyanotic children after congenital heart surgery (Chakravarti et al., 2009). The averaged cerebral and renal rS02 was a good predictor of the lactate status, with a value less than or equal to 65%, predicting a lactate level of greater than or equal to 3.0 mmol/L (27 mg per dL), with a sensitivity of 95% and a specificity of 83% in the studied patients. Consequently, monitoring of rS02 could aid in the prompt identification of patients at risk for hyperlactatemia and low-cardiacoutput syndrome (Chakravarti et al., 2009). A combination of cerebral and renal rS02 with an average value less than 65% using the intravenous NIRS device could, therefore, predict hyperlactatemia (>3 mmol/L (>27 mg/dL)) in acyanotic children after congenital heart surgery.

Patients with higher blood lactate levels during CPB were also more likely to have myocardial infarction and postoperative neurologic, hemodynamic, pulmonary, digestive, or renal complications (Demers et al., 2000).

Moreover, sepsis as postoperative complication, can be the cause for late postoperative hyperlactatemia.

#### **5.3 Summary**

Patients without signs of clinical shock can still be hypoperfused and are at high risk for preperi- and postoperative complications. They tend to develop postoperative hyperlactatemia. Patients undergoing surgery with a RACHS-1 score of IV and higher are not expected to maintain good cardiac output in the postoperative period, emphasizing the importance of combining pre- peri- and postoperative prognosis predictors, especially for the so called "preoperative good prognosis" groups.
