Nithyakala P, Dharsshini N, Dhivya Bharathi
S, Hamsavarthini S, Indhu Malini N
Swamy Vivekanandha College of Pharmacy, Namakkal, Tamil Nadu,
India
Abstract
The normal range of lactate is 0-2mmol/L and value above it is
considered as hyperlactatemia. It may arise due to adequate
and inadequate oxygen supply mechanisms. The major reason is
likely a stress-induced aerobic mechanism which shows raised
levels of lactate. Increased lactate levels can cause
acidifying effects on the blood. There are many etiological
reasons for lactic acidosis like disease conditions,
deficiency and alcohol. Early and late onset are two
categorizations for patients with hyperlactatemia after
cardiac surgery. One of the major trigger factors for lactic
acidosis in cardiopulmonary surgery patients is tissue
hypoperfusion. So preventive measures before cardiac surgery
should be taken.
Introduction
In patients undergoing heart surgery, lactate level is a
crucial biomarker and an excellent predictor of treatment
results. In a number of studies, hyperlactatemia (HL) is a
reliable indicator of mortality and serious morbidity
following cardiac surgery [1]. In accordance with the
underlying cause, Cohen and Woods separated lactic acidosis
into two groups: lactic acidosis accompanied by or not by
symptoms of tissue hypoxia [2]. Oxygen deprivation may be the
result of insufficient blood flow brought on by a decline in
cardiac output, a reduction in haemoglobin levels, or a
problem with target cells' ability to absorb oxygen. In order
to diagnose and evaluate hypoxia and lactic acidosis in those
who are in cardiac failure, the level of blood lactate is
measured. Hyperlactatemia is a typical metabolic syndrome
following heart surgery with cardiopulmonary bypass. Its
mechanism is intricate and debatable. The most frequent factor
causing hyperlactatemia is tissue hypoxia (type A). According
to research, type B (absence of tissue hypoxia) could be an
additional factor in the development of hyperlactatemia after
heart surgery. It has been demonstrated in several
investigations that hyperlactatemia can be adrenaline induced.
This mechanism is known as aerobic glycolysis. This type of
glycolysis is a stress response rather than due to oxygen
shortage [3].
In one of the studies after cardiac surgery, HL was detected
in 1 in 10-20 percent of the overall of adult patients, and it
was linked to severe postoperative morbidity and death.
According to a research by Broder and Weil, there was a high
probability of circulatory shock-related death in more than
88% of patients with blood lactate levels more than 4.0
mmol/L. The chances of surviving shock decrease from 90%
to 10%, as stated by the same authors, when lactate levels in
the blood rose from 2.0 to 8.0 mmol/L. In hospitals and
intensive care units, serum lactate levels are often utilized
as a guidance for doctors to initiate and enhance early
therapy in shock patients and so aid to reduce morbidity and
mortality. Despite having normal arterial blood gases (ABG),
individuals after heart surgery under cardiopulmonary bypass
(CPB) may still have lactic acidosis as a result of tissue
hypoperfusion. Consequently, monitoring lactate levels in
individuals undergoing heart surgery may be more sensitive
than ABG measurement alone and may subsequently help in early
diagnosis of an imbalance between demand and supply of oxygen
[4].
Although lactic acidosis can have a number of different
causes, having elevated serum lactate levels after heart
surgery has been linked to an elevated chance of postoperative
infection, cardiopulmonary dysfunction, renal impairment,
longer hospital stay, and higher mortality. It has been
established that aiming for normal lactate levels in the
postoperative setting can shorten hospital stays after heart
surgery [5].
However, as per recent research, not all types of HL are
detrimental following cardiac surgery. In contrast to patients
who developed hyperlactatemia later after surgery, Maillet and
colleagues observed that the timing of HL plays a significant
effect and that individuals with an immediate postoperative
elevated lactate level have much worse results. As a result,
the clinical results following heart surgery may be affected
differently depending on the onset of hyperlactatemia (early
versus late) [1]. This article aims to summarise the
information on the etiology of hyperlactataemia during cardiac
surgery, provide an explanation of lactate physiology as it
relates to the field of cardiac surgery, and demonstrate the
intricate connection between the development of HL and patient
outcomes.
Pathophysiology
Category of Hyperlactatemia
There are two major types of lactic acidosis: Type A, caused
by a lack of oxygen, and Type B, irrespective of that, seems
to be sufficient oxygen supply [6]. Type A lactic acidosis is
defined by poor tissue oxygenation, whereas Type B lactic
acidosis is defined by a low level of tissue hypoxia. A high
lactate to pyruvate (L/P) ratio is frequently linked to type A
lactic acidosis, which indicate either a global or local
deficiency of tissue oxygen transport. Hepatic, mesenteric,
and limb ischemia are three causes of limited oxygen
transport. An expected L/P ratio is linked to Type B lactic
acidosis, which is characterized by rapid aerobic metabolism.
Drug overdose and poisonings (cyanide, methanol, salicylates),
ketoacidosis due to diabetes, hepatic malfunction (reduced
lactate clearance), and thiamine insufficiency (impaired
pyruvate dehydrogenase function) are additional reasons of
Type B acidosis. Depending on a specific aetiology, the L/P
ratio might be normal or high [7].
Important Causes of Hyperlactatemia
Seizure
Depending on the category of seizure, lactate levels may be
dramatically raised. It is very important for the physician to
understand that higher levels of lactate in this situation are
sporadic. Once the episode has passed, lactate is no longer
produced and is quickly eliminated. Extended periods of time
with persistently high lactate levels after having a seizure
may indicate a distinct or concurrent base etiology and
require for additional examination [8, 9].
Diabetic Ketoacidosis
Elevated lactate levels may develop in diabetic ketoacidosis
(DKA), a condition that is not commonly noticed, but unlike
other disease states, they do not appear to be related to more
serious outcomes [5]. In a historical analysis of 68
individuals with DKA, Cox et al. discovered that 40% had
lactate levels above 4 mmol/L. There was no association
between lactate and mortality or duration of stay in the
intensive care unit in this group. It is possible that
elevated lactate levels in DKA may be caused by both a changed
metabolic profile and hypoperfusion, which is indicated by the
fact that lactate levels have a positive relationship with
glucose and a poor relationship with thiamine levels. However,
additional study is needed [10,11].
Malignancy
Individuals with rapidly progressing leukaemia or lymphoma,
usually affecting the liver, are a majority of cancer patients
who appear with high levels of lactate that are linked to
their disease. Although the aetiology is unclear, it is
probably linked to the excessive production of glycolytic
enzymes by tumors, mitochondrial malfunction, decreased
hepatic clearance, and possibly malnutrition, which results in
thiamine deficiency [12, 13].
Burns
Lactate had been identified to be a powerful indicator of
prognosis in cases of serious burns. According to Jeng et al.,
the very first lactate point was a helpful variable to
distinguish between survivors and nonsurvivors [14]. Similar
outcomes were observed in one more prospective trial by Kamolz
et al applying an early lactate limit of 2 mmol/L.
Additionally, they demonstrated a link between immediate
lactate elimination and reduced mortality [15].
In addition, sepsis with multi-organ dysfunction is a
significant cause of morbidity and mortality in burns
patients. When working with burns patients, lactate levels
should be acquired and taken into account, though its utility
in terms of therapeutic outcome is uncertain [16].
Thiamine Deficiency
Thiamine acts as a coenzyme for a number of cellular enzymes,
such as pyruvate dehydrogenase and alpha ketoglutarate
dehydrogenase, which are necessary for the tricarboxylic acid
cycle and aerobic glucose metabolism, respectively. Thiamine
deficiency supports anaerobic metabolism, which results in
higher lactate generation. Thiamine deficiency has been linked
to the formation of increased lactate levels in blood and
cerebrospinal fluid. States of nutritional deficit, such as
alcoholism, persistent atrophy disorders, hyperemesis
gravidarum, anorexia nervosa, and gastric bypass surgery, are
risk factors for thiamine deficiency. When there is no other
explanation for high lactate levels, it is important to take
into account the frequently neglected but treatable condition
of thiamine deficiency [17].
Lactulose
Lactate and acetate are produced in the intestines from
synthetic, nondigestible disaccharide known as lactulose. The
colonic epithelium may receive lactate if excessive amounts of
lactulose are given, or if lactulose is retained in the gut,
leading to systemic L- and D-hyperlactatemia. Lactulose
administration to healthy individuals only causes slight
elevations in plasma L- and D-lactate [18].
Carbon Monoxide
Carbon monoxide attaches to haemoglobin with a higher affinity
than oxygen, and forms carboxyhemoglobin preventing efficient
oxygen transport [19]. In addition to lowering oxygen supply
by shifting the oxyhemoglobin curve to the left, carbon
monoxide also causes oxidative stress and direct cellular
injury [19]. The primary cause of hyperlactatemia from carbon
monoxide poisoning is assumed to be tissue hypoxia [20].
Alcohol
The relationship between increased lactic levels and alcohol
is still uncertain, and studies have produced conflicting
findings. Despite the fact that ethanol may raise lactate
levels in an experimental environment, clinically significant
elevated lactate levels are uncommon in healthy individuals.
Lactate level increase should not be ascribed only to the
possible effects of ethanol; rather, other reasons of highly
raised lactate levels in these patients should be ruled out
and treated if present. Patients who consume alcohol may be
more susceptible to other conditions that raise lactate
levels, such as a lack of thiamine, convulsions, sepsis, and
other harmful substances. In addition to ethylene glycol
toxicity, increased lactate levels have also been linked to
other alcohols like propylene glycol and methanol [17].
Hyperthyroidism
Through amplification of glycolysis and the hexose
monophosphate pathway, hyperthyroidism increases basal
metabolic rate, which in turn increases glucose metabolism and
hyperlactatemia. In addition, due to the loss of thiamine
reserves, hyperthyroidism and thyroid storm can be considered
as risk factors for thiamine deficiency [18].
Propofol
Acute metabolic acidosis, heart failure, rhabdomyolysis,
lipemia, and hepatomegaly or hepaticlipidosis are all symptoms
of propofol infusion syndrome, also known as PRIS [21].
Renal failure, lactic acidosis, and hyperkalemia are
additional frequent features of this condition [22]. People
who receive propofol for extended periods of time are more
likely to develop PRIS. The two main pathophysiologic
processes for PRIS are thought to be impaired fatty acid
oxidation and mitochondrial malfunction [23,24].
Lactic Acidosis After Cardiac Surgery
There are numerous studies which mention the link between
cardiac surgery and lactic acidosis. The etiological factors
may include both hypoxic and non-hypoxic causes. Usual normal
range of serum lactate is 0-2 mmol/L, but the reference
range is 0.75-2mmol/L. Higher levels have been associated with
in hospital mortality [25]. Increased lactate levels are
observed during or immediately following the start of
cardiopulmonary bypass, and in the following 4-24 hours of the
postoperative intensive care unit (ICU) stay. In 10 to 21% of
patients having on-pump cardiac surgery, HL develops during or
shortly after CPB and commonly lasts until ICU arrival which
is called as "Immediate hyperlactaemia" (IHL) or Early Onset
Hyperlactaemia. For cardiac anaesthia and intensive care
clinicians, it is an important finding that frequently prompts
worries about a challenging intra or postoperative course.
Late-onset HL (LHL) is a condition that has been linked to
cardiac surgery. Observational data shows elevated lactate
of 4 to 14 hours after operation, which returns to
normal within 12 to 24 hours [18, 26-28]. Following both
emergency and elective cardiac surgery, this happens in 14-20%
of adult patients. Perfusion deficits are produced while using
cardiopulmonary bypass in the group of people who have had
cardiac surgery specifically, as perfusion of the organs is
insufficient for demand if core temperature rises under CPB.
Lactate levels >10 mmol/l at early time was found to have a
100% positive predictive value in a retrospective small study,
that indicated postoperative mortality. Liver failure
contributed in some patients' elevated systemic lactate
levels. Longer CPB duration and decreased oxygen supply (DO2)
during CPB were independent risk factors for development of
hyperlactatemia. Circulatory dysfunction is evident even in
critically ill surgical patients, according to Meregalli et
al., who also claimed that there is no sign of shock in these
patients. It is assumed that the presence of hyperlactatemia
suggests "occult hypoperfusion" in some patients, which would
account for their higher mortality [29].
Studies and Reports
A strong predictor and a reliable biomarker in open-heart
surgery and critically ill patients is Lactate [30-33]. Modern
technological developments have helped to increase the number
of cardiac surgeries. While treating the patients who have
already undergone cardiac surgery, identifying risk factors
for mortality and disability are crucial. In individuals with
systemic hypoperfusion, hypoxia, metabolic acidosis and
hyperlactatemia are frequent events [34]. In 2014, Marjan
Joudi et.al conducted a descriptive study among 228 patients
where the findings demonstrated that among the variables
assessed, the number of blood transfusions, ejection fraction
(EF) prior to surgery, diabetes mellitus, length of time using
a pump, and blood storage time, respectively, significantly
increased postoperative serum lactate compared to
pre-operative levels [35]. A retrospective study conducted by
Maket al. in 195 cardiac surgery patients undergoing bypass
and/or valve surgery. They have concluded that patients who
have undergone cardiac surgery who hadt late peaking blood
lactate >30 h post-operatively are more likely to have a
poor outcome in the intensive care unit and die. In post-CPB
patients, lactate persistence is a better indicator of
prognosis than peak lactate. In contrast to a simple post-CPB
lactate washout, patients in a condition of prolonged
hypoperfusion are more likely to experience serious surgical
complications and die [36].
Renew et al., in 2016 reported that 121 (1.26%) of the 9580
cardiac surgery patients who satisfied the inclusion criteria
developed HL and cardiogenic shock was the most frequent
reason (53.8%). In that study, a total of 49 (40.5%) patients
passed away while receiving care and 40 (33.1%) were sent
home. The remaining 32 (26.4%) patients were transferred to a
skilled-care institution [34].
More research is necessary to fully understand these findings,
especially how persistent hyperlactatemia affects
decision-making in this complicated patient population.
Conclusion
The majority of the patients who undergo heart surgery are
likely to develop both hypoxia and non-hypoxia conditions
which can cause hyperlactatemia. Most likely, stress-induced
increased oxygenated metabolism, where the higher lactate
emerges from a cumulative effect on the lactate or pyruvate
equilibrium, is the main non-hypoxic cause. It is crucial to
keep in mind, nevertheless not all postoperatively developed
de novo hyperlactatemia is benign. Hyperlactatemia and
acidosis are common features of complications like cardiac
arrest, septic shock and ischemia brought on by myonecrosis or
mesenteric infarction. Routine monitoring should be done in
the intensive care unit to ensure that the patient is not at
risk of developing hyperlactatemia and also we should be
attentive to maintain normotensive and normovolemic
hemodynamic status.
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