Which Neurological clinical manifestations are associated with metabolic acidosis?

Disorders of Acid–Base Balance

Disorders of acid–base balance are classified according to their cause, and the direction of the pH change, into respiratory acidosis, metabolic acidosis, respiratory alkalosis, or metabolic alkalosis. [7,8; reference 8 also includes illustrative case studies] Any derangement of acid–base balance elicits compensatory changes in an attempt to restore homeostasis (Figure 37.8). Acidosis due to respiratory failure leads to compensatory renal changes, which lead to increased reclamation of HCO3−.

In the assessment of acid–base disorders, commonly measured electrolytes are serum Na+, K+, H+ (as pH), Cl−, and HCO3−. Other anions (e.g., sulfates, phosphates, proteins) and cations (e.g., calcium, magnesium, proteins) are not measured routinely but can be estimated indirectly, since (to maintain electrical neutrality) the sum of the cations must equal that of the anions. Serum Na+ and K+ content accounts for 95% of cations, and Cl− and HCO3− for about 85% of anions.

Unmeasuredanions=[Na+]+[K+]−[Cl−]−[HCO3−]

The unmeasured anion is commonly known as the anion gap, which is normally 12±4 mEq/L. This value is useful in assessing the acid–base status of a patient and in diagnosing metabolic acidosis. Disorders that cause a high anion gap are metabolic acidosis, dehydration, therapy with sodium salts of strong acids, therapy with certain antibiotics (e.g., carbenicillin), and alkalosis. A decrease in the normal anion gap occurs in various plasma dilution states, hypercalcemia, hypermagnesemia, hypernatremia, hypoalbuminemia, disorders associated with hyperviscosity, some paraproteinemias, and bromide toxicity.

The urinary anion gap (UAG) is utilized in the diagnosis of metabolic acidosis caused by defects in renal reclamation of bicarbonate. As discussed previously, renal acid excretion requires urinary excretion of NH4+ and its accompanying Cl− ions. Thus Cl− concentration is used as a surrogate level of NH4+ in the UAG calculation, along with urinary Na+ and K+ concentrations, as follows:

UAG=(Na++K+)−Cl−

In metabolic acidosis due to bicarbonate loss in chronic diarrhea, renal compensation leads to an increased level of NH4+, and therefore Cl− excretion, resulting in a negative UAG; whereas in disorders of primary renal acidification systems, the UAG has a positive value.

Respiratory acidosis is characterized by the accumulation of CO2, a rise in P CO2 (hypercapnia or hypercarbia), a decrease in [HCO3−]/[ PCO2], and a decrease in pH (see the Henderson–Hasselbalch equation, Chapter 2). It may result from central depression of respiration (e.g., narcotic or barbiturate overdose, trauma, infection, cerebrovascular accident) or from pulmonary disease (e.g., asthma, obstructive lung disease, infection). Increased [H+] is, in part, buffered by cellular uptake of H+ with corresponding loss of intracellular K+. In acute hypercapnia, the primary compensatory mechanism is tissue buffering. In chronic hypercapnia, the kidneys respond to elevated plasma PCO2, increasing the amount of HCO3− formed by carbonic anhydrase in the tubules and by excreting more H+. The primary goal of treatment is to remove the cause of the disturbed ventilation. Immediate intubation and assisted ventilation also aid in improving gas exchange.

Metabolic acidosis [9,10] with increased anion gap occurs in diabetic or alcoholic ketoacidosis; lactic acidosis from hypoxia, shock, severe anemia, alcoholism, or cancer; toxicity from ingestion of salicylates, methanol, paraldehyde, or ethylene glycol; and renal failure. Lactic acid acidosis caused by deprivation of tissue oxygen, inhibition of gluconeogenesis, and some drugs and toxins is due to the accumulation of L-lactate, which is the end product of glycolysis (Chapter 12). Frequently, L-lactate (simply referred to as lactate) is the metabolite measured in assessing metabolic acidosis. However, D-lactate may be produced under certain clinical conditions, such as diminished colonic motility, short bowel syndrome, jejunoileal bypass, overgrowth of D-lactate producing gram-positive organisms (e.g., Lactobacillus species, Streptococcus bovis). Carbohydrate malabsorption and ingestion of large amounts of carbohydrates may also exacerbate the development of D-lactate acidosis. In addition, an impairment of D-lactate metabolism may also contribute to D-lactic acidosis. D-lactate is converted to pyruvate by D-2-hydroxy acid dehydrogenase, a mitochondrial enzyme present in liver, kidney, and other tissues. The clinical manifestations of D-lactic acidosis include episodes of encephalopathy and metabolic acidosis. Since serum D-lactate is not normally a measured clinical parameter, the critical indices of suspicion of D-lactic acidosis in the clinical conditions mentioned previously include increased anion gap metabolic acidosis with negative tests for L-lactate and ketoacidosis. Metabolic acidosis with normal anion gap occurs in renal tubular acidosis, carbonic anhydrase inhibition, diarrhea, ammonium chloride administration, chronic pyelonephritis, and obstructive uropathy. In both of these groups, plasma HCO3− levels decrease and tissue buffering occurs by exchange of extracellular H+ for intracellular K+. Thus, plasma K+ levels may increase.

Metabolic acidosis produces prompt stimulation of respiratory rate and a decrease in PCO2. This effect cannot be sustained, however, because the respiratory muscles become tired. Renal compensation is slower but can be maintained for an extended period because of induction of glutaminase.

Treatment is by correction of the cause of the acidosis (e.g., insulin administration in diabetic ketoacidosis) and neutralization of the acid with NaHCO3, sodium lactate, or TRIS [tris(hydroxymethyl)aminomethane] buffer. Problems that may occur following alkali replacement therapy include development of respiratory alkalosis, particularly if the low CO2 tension persists, and further decline in the pH of CSF, which may decrease consciousness. The alkaline “overshoot” results from resumption of oxidation of organic anions (e.g., lactate, acetoacetate) with the resultant production of bicarbonate from CO2. Severe acidosis should be corrected slowly over several hours. Potassium replacement therapy is frequently needed because of the shift of intracellular K+ to extracellular fluid and the loss of K+ in the urine.

Respiratory alkalosis occurs when the respiratory rate increases abnormally (hyperventilation), leading to a decrease in PCO2 and a rise in blood pH. Hyperventilation occurs in hysteria, pulmonary irritation (pulmonary embolus), and head injury with damage to the respiratory center. The increase in blood pH is buffered by plasma HCO3− and, to some extent, by the exchange of plasma K+ for intracellular H+. Renal compensation seldom occurs, because this type of alkalosis is usually transitory.

Metabolic alkalosis is characterized by elevated plasma HCO3− levels. It may result from the administration of excessive amounts of alkali (e.g., during NaHCO3 treatment of peptic ulcer) or of acetate, citrate, lactate, and other substrates that are oxidized to HCO3−, and from vomiting, which causes loss of H+ and Cl−.

In excessive loss of extracellular K+ from the kidneys, cellular K+ diffuses out and is replaced by Na+ and H+ from the extracellular fluid. Since K+ and H+ are normally secreted by the distal tubule cells to balance Na+ uptake during Na+ reabsorption (see Figure 37.3), if extracellular K+ is depleted, more H+ is lost to permit reabsorption of the same amount of Na+. Loss of H+ by both routes causes hypokalemic alkalosis. Excessive amounts of some diuretics and increased aldosterone production can cause the hypokalemia that initiates this type of alkalosis.

In compensation, the respiratory rate decreases, raising PCO2 and lowering the pH of blood. This mechanism is limited because if the respiratory rate falls too low, PO2 decreases to the point where respiration is again stimulated. Renal compensation involves decreased reabsorption of bicarbonate and formation of alkaline urine. Because the urinary bicarbonate is accompanied by Na+ and K+, if the alkalosis is accompanied by extracellular fluid depletion, renal compensation by this mechanism may not be possible. Treatment consists of fluid and electrolyte replacement and NH4Cl to counteract the alkalosis.

Acid–base disturbances frequently coexist with two or more simple disorders. In these settings, blood pH is either severely depressed (e.g., a patient with metabolic acidosis and respiratory acidosis) or normal. Both plasma HCO3− and pH may be within normal limits when metabolic alkalosis and metabolic ketoacidosis coexist, as in a patient with diabetic ketoacidosis who is vomiting. In this situation, an elevated anion gap may be the initial abnormality that can be detected in the underlying mixed acid–base disturbance. Acetylsalicylate (aspirin) toxicity causes metabolic acidosis and respiratory alkalosis. The latter is due to the stimulation of respiratory centers, resulting in hyperventilation and decreased PCO2.

Therapy and Prognosis

Dehydration and acid/base imbalances should be corrected before surgery. Perioperative antimicrobials should also be administered. The calf is restrained in left-lateral recumbency and an exploratory celiotomy performed in the right flank under local or general anesthesia. The affected bowel is exteriorized, and the intussusception manually reduced if possible. Depending on the type of intussusception, cecal amputation (see Chapter 14 for details on cecal amputation) and resection of the ileum and proximal loop of the ascending colon may be indicated (Figure 17-19). The high recurrence rate of intussusception necessitates cecum amputation, even if the compromised bowel is viable. The ileocecal junction is left intact if it is not compromised by the intussusception. Postoperative measures include correcting electrolytes, acid/base, and energy imbalances/losses and aggressively treating the primary disease (for example, diarrhea).

The prognosis is guarded after treating cecal intussusception because affected calves are frequently in poor general condition before surgery. Rate of survival is mainly influenced by the prognosis for the concurrent diarrhea.

Summary

Defense against acid–base imbalance is accomplished through three interacting systems: the chemical buffers of the blood, the respiratory system, and the renal system.

The chemical buffers resist changes in plasma pH by binding H+ ions when they are in excess and dissociating to form H+ ions when the [H+] falls. The most important chemical buffer is the HCO3− buffer because it can be adjusted by both the respiratory and renal systems.

The respiratory system adjusts plasma pH by adjusting PaCO2 . During acidosis, respiration is stimulated, resulting in decreased PaCO2 . According to the Henderson–Hasselbalch equation:

pH=6.1+log([HCO3−]/0.0308PaCO2)

decreasing PaCO2 increases the pH. Thus acidosis evokes a compensatory respiratory alkalosis. Similarly, alkalosis inhibits respiration so that PaCO2 rises, and the acidosis is countered by a respiratory compensation.

The respiratory compensation is never complete because there must be residual pH imbalance to maintain the respiratory response that elevates or reduces Pa CO2. The renal compensation, however, is complete. The renal system adjusts pH by either excreting HCO3− by failing to reabsorb all of the filtered HCO3− or by forming new HCO3− linked to the excretion of titratable acid or NH4+. The main activity of the kidneys is to secrete H+ through either an H+-ATPase or an Na+–H+ exchanger located on the apical membrane. Secreted H+ then either combines with filtered HCO3−, or with filtered buffers such as Na2HPO4, or with NH3. Every secreted H+ causes HCO3− to appear in the plasma. Thus when secreted H+ ions combine with filtered HCO3−, the overall process is equivalent to reabsorption of filtered HCO3 −; when H+ combines with titratable acid or NH3, the kidney effectively places new HCO3 in plasma.

Thus the kidney can excrete HCO3− in an alkaline urine, thereby reducing the [HCO3−] in blood. By the Henderson–Hasselbalch equation, this would lower blood pH. Alternatively, the kidney can fight acidosis by adding HCO3 − to blood, alkalinizing the blood while excreting an acid urine.

24 What preoperative tests are required before induction?

Special emphasis should be placed on correcting the acid-base and electrolyte imbalance during the acute phase. Therefore an arterial blood gas analysis and a chemistry panel are suggested. In the presence of CO poisoning, the pulse oximeter may overestimate the saturation of hemoglobin; therefore a COHb level, determined by co-oximetry, may be helpful to assess the degree of the CO poisoning and to guide treatment. Coagulation tests are also helpful, because such patients often have bleeding diathesis. A urine myoglobin should be done in patients with a history of electrical injury or pigmented urine.

TREATMENT

Treatment involves correcting energy, electrolyte, and acid-base imbalances, as well as stimulating appetite and treating dehydration. Females should be offered a palatable, energy-rich, highly digestible feed stuff. In the early stages of disease (animal still ambulatory), females may be treated with oral or intravenous glucose, balanced electrolyte solution with additional calcium (25 ml of a 23% calcium borogluconate per liter), potassium chloride (10-20 mEq/L), 5% dextrose, and sodium bicarbonate. Propylene glycol can be administered (15-30 ml every 12 hours) as a glucose precursor. Supplementation with vitamin B complex and transfaunation with rumen liquor may help stimulate appetite. In the later stages of disease, when the animal is recumbent, the prognosis is poor and treatment must be aggressive. The aforementioned treatments must be initiated immediately, and removal of the fetuses is crucial.3 Treatment usually involves cesarean section or induction of parturition and is aimed at saving the life of the dam at the expense of the lambs or kids. Lambs or kids born more than 7 days premature seldom survive.2

4.2 Adult Effects

For most adult marine species of fish, acid–base imbalances are tolerated via homeostatic adjustments of bicarbonate accumulation and ion exchange across the gills (Claiborne et al., 2002). Teleosts, in general, can adapt to prolonged elevation of CO2 saturations through acid–base regulation and by increasing ventilation frequencies, thereby avoiding internal acidosis (Ishimatsu et al., 2005, 2008). However, not all fish species demonstrate the same capacity of tolerance or compensation for pH imbalance, nor do all life stages. Regardless of a species’ tolerance to lower pH or the capacity to compensate for any internal acid–base disturbances, acidic environmental conditions generally result in a depressed metabolic performance in both invertebrate and vertebrate organisms (Fabry et al., 2008; Pörtner et al., 2004). Features of acid–base and gas properties of arterial blood were examined in the squid, Illex illecebrosus, and it was found that pH was a critical driver in the relationship between O2 binding, oxygen partial pressure (PO2), and blood pH (Pörtner et al., 2004). Effects of OA can be particularly harmful to marine calcifiers that rely heavily on pH for baseline physiological performance and survival (Pörtner et al., 2004). For example, the blue mussel Mytilus edulis, regulates internal pH by suppressing metabolism and dissolving their carbonate shell when exposed to increased CO2 levels (Bibby et al., 2008; Gazeau et al., 2007). Additionally, the work by Bibby et al. (2008) found that with increased acidity, the cellular immune response mechanism, hemocytic phagocytosis, was significantly reduced in M. edulis. With the potential for future OA to be harmful for invertebrates by itself, the interaction with other anthropogenic factors, including EDCs could likely alter their toxicity and change the sensitivity of organisms toward these stressors (Fabry et al., 2008; Freitas et al., 2015).

Interactions between toxicants and ecologically relevant levels of OA have been understudied in aquatic ecosystems. With GCC-induced OA becoming a major and present concern, more mechanistic studies are needed to address the possible interactions between EDCs and environmental stressors. Analysis on biologically harmful metals by Millero et al. (2009) found that decreases in concentration of OH− and CO2− ions can directly affect chemical and physical properties including solubility, adsorption, toxicity, and rates of redox reactions metals in seawater. Such outcomes will have a great potential to alter the availability and toxicity of metals to marine organisms (Millero et al., 2009). Processes associated with contaminant exposure such as bioaccumulation and elimination of endocrine disruptive flame retardants have been shown to be increased acidic conditions in two estuarine bivalve species, the Japanese carpet shell clam Mytilus galloprovincialis and Ruditapes philippinarum (Maulvault et al., 2018b). However, it is hypothesized that the majority of the physiological effects are due to exposure to increased aquatic CO2 saturation (environmental hypercapnia) rather than lower ambient pH (Ishimatsu et al., 2004).

Preus-Olsen et al. (2014) proposed that the ecological context may amplify climate-EDC impacts markedly among inbred species and populations that occupy narrow niches with limited genetic diversity (e.g., threatened or endangered species) or those that display environmental sex determination. They examined combined exposure to perfluorooctane sulfonic acid (or sulfonate; PFOS) and elevated levels of CO2 saturation in juvenile Atlantic cod (Gadus morhua). PFOS is a persistent organic pollutant (POP) that is detected globally and associated with numerous adverse health effects, including endocrine disruption (Kannan, 2011; Lau et al., 2007). Preus-Olsen et al. (2014) measured concentrations of sex steroid hormones and estrogenic responses and found that combined PFOS and hypercapnia exposure (0.3% increase in CO2) produced increased effects on steroid levels as compared to hypercapnia alone (Preus-Olsen et al., 2014; Fig. 4). What is yet to be fully understood is the mechanisms that underlies any additive relationship between OA and chemical pollutants. Further multi-stressor studies should be conducted for conservation management and a better understanding of ecophysiology in marine ecosystems.

E Mixed Acid-Base Imbalances

Mixed acid-base disorders occur when several primary acid-base imbalances coexist (de Morais, 1992a). Metabolic acidosis and alkalosis can coexist and either or sometimes both of these metabolic abnormalities may occur with either respiratory acidosis or alkalosis (Nairns and Emmett, 1980; Wilson and Green, 1985). Evaluation of mixed acid-base abnormalities requires an understanding of the anion gap, the relationship between the change in serum sodium and chloride concentration, and the limits of compensation for the primary acid-base imbalances (Saxton and Seldin, 1986; Wilson and Green, 1985). Clinical findings and history are also necessary to define the factors that may contribute to the development of mixed acid-base disorders. The following are important considerations in evaluating possible mixed acid-base disorders:

Compensating responses to primary acid-base disturbances do not result in overcompensation.

With the possible exception of chronic respiratory acidosis, compensating responses for primary acid-base disturbances rarely correct pH to normal. In patients with acid-base imbalances, a normal pH indicates a mixed acid-base disturbance.

A change in pH in the opposite direction to that predicted for a known primary disorder indicates a mixed disturbance.

With primary acid-base disturbances, bicarbonate and pCO2 always deviate in the same direction. If these parameters deviate in opposite directions, a mixed abnormality exists.

Although mixed acid-base abnormalities undoubtedly occur in animals and have been documented in the veterinary literature, they are often overlooked (Wilson and Green, 1985). An appreciation of the potential for the development of mixed abnormalities is essential for the correct interpretation of clinical and clinicopathological data, which would otherwise be quite confusing. Care should be taken when evaluating suspected mixed acid-base abnormalities that sufficient time has elapsed so that anticipated compensating responses could have occurred (de Morais, 1992a).

Summary

When one approaches a critically ill child with an acid-base imbalance, the first step is to define the nature of the disorder: acidosis versus alkalosis, acidemia versus alkalemia, simple versus mixed, acute versus chronic, severe and harmful versus neither severe nor harmful. The available tools for answering these questions are numerous. The easiest way to screen the acid-base status is to take a glimpse at venous bicarbonate (or CO2TOT) concentration. However, a normal concentration (22 to 26 mEq/L) does not rule out the possibility of an acid-base derangement. So, if the clinical setting raises the suspicion of an illness known to be associated with acid-base imbalances, at the very least plasma electrolyte concentrations must be obtained, along with albumin levels, to calculate the AGCORR. If bicarbonate (or CO2TOT) or AGCORR is abnormal, or a complex, potentially harmful, mixed acid-base disorder is suspected, an arterial blood analysis must be done, which will provide information on pH, Paco2, and SBE. The classical bicarbonate-centered observational patterns must be applied. If available, lactate levels must be obtained too. This is mandatory if metabolic acidosis exists (with or without acidemia). If there is the suspicion of the presence of unmeasured anions and/or a mixed acid-base problem, it is advisable to calculate SIDAPP, SIDEFF, and SIG, to delve deeper into the possible pathophysiological mechanisms underlying the acid-base unbalance. Care must be taken to review the patient’s history for hemodynamic resuscitation with large volumes of normal saline solutions. If that is the case, special attention must be given to chloride levels and to analyzing the effect of the different components of acid-base physiology on SBE (“partitioned SBE”). The severity, potential harm of the acid-base derangement, and probable therapeutic intervention must be all defined. There is compelling evidence that abnormal pH by itself may not be as dangerous as once thought. However, an individualized approach must be taken in order to decide if a given patient has the chance of benefit or not from the attempt to modify his/her pH and acid-base status.

References are available online at http://www.expertconsult.com.

Noncardiac Causes of Ventricular Tachycardia

Ventricular cells are sensitive to hypoxemia, electrolyte and acid-base imbalances, sympathetic stimulation, and various drugs. These changes typically affect the passive and energy-dependent ion exchanges across the cellular membrane of the myocyte during the initiation and propagation of the action potential.

Hypokalemia is the most commonly reported electrolyte disturbance responsible for or contributing to VT. It increases phase 4 depolarization, increasing spontaneous automaticity, and prolongs the action potential duration, which promotes arrhythmias from triggered activity.5 Because digoxin competes with potassium on its receptors, hypokalemia increases the risk of digoxin toxicity. Similar arrhythmias result from hypomagnesemia, because magnesium is necessary for proper functioning of the sodium-potassium ATP pump, which maintains normal intracellular potassium concentration. Hypocalcemia and hypercalcemia are also responsible for ventricular arrhythmias.

Increased adrenergic tone potentiates arrhythmias through various mechanisms. In the intensive care unit, drugs with sympathetic or sympatholytic activity are used commonly and should be stopped when possible to assess their role in the perpetuation of VT.

It is also important to evaluate the potential proarrhythmic effects of all the medications given to a patient with VT. There are many publications on drug-induced prolongation of the QT segment. Prolongation of the QT segment reflects prolongation of the cardiac cell membrane repolarization and indicates a risk of ventricular arrhythmia from triggered activity. Antiarrhythmic drugs such as procainamide and sotalol, but also domperidone, cisapride, chlorpromazine, and erythromycin, are known to prolong the QT segment. Bradycardia and hypokalemia contribute to this effect on repolarization and increase the risk of VT.6

Oxygen therapy, identification and correction of all electrolyte disturbances, and discontinuation of proarrhythmic medications are the initial and necessary first steps in the treatment of all patients with VT.

Treatment

Initial treatment is supportive with the goal of correcting hydration, acid–base and electrolyte imbalances, and hypoglycaemia.

Intravenous fluids. There are many options on the market, but balanced isotonic replacement solutions such as lactated Ringer's solution, Plasma-Lyte 148, Normosol R, or Isolyte S are good initial options. Saline solution (0.9%) can be used in some cases. Another aspect to consider when using these solution is the pH; while replacement solutions have a pH of >6.0, pH of 0.9% saline solution is 4.0. This may be relevant in foals with metabolic acidosis.

Administration of KCl should be considered in severe hypokalaemia. KCl administration should not exceed 0.25–0.5 mEq/kg/h as a rapid rate may lead to cardiac dysrhythmias. Mild hypokalaemia is often corrected with restoration of the hydration status, and intravenous or oral supplementation of KCl may not be necessary.

Supplementation becomes more important in foals with metabolic acidosis, as low pH leads to overestimation of serum K concentrations. As the pH increases K moves into the cells and vice versa.

Severe acidosis may require intravenous administration of isotonic sodium bicarbonate. It is preferable to administer sodium bicarbonate alone than to mix it with other solutions, in particular those with calcium and magnesium salts as they may precipitate. Rapid administration of sodium-containing fluids to foals with severe hyponatraemia may lead to neurological signs.

Dextrose may be added to fluids for hypoglycaemic foals. Typical solutions include 5% dextrose or 2.5% dextrose + 0.45% saline. Dextrose can also be added to other solutions to create a 2.5–5% concentration. Injectable hypertonic dextrose comes as a 25% or 50% solution.

Hypocalcaemia is a frequent abnormality in foals with gastrointestinal disease. Isotonic solutions can be supplemented with calcium gluconate (23%) at 10 mL/L.

Oral electrolyte solutions.

Not as effective in correcting severe electrolyte and acid–base imbalances, especially if absorption is impaired from enteritis. However, oral supplementation of potassium chloride and sodium bicarbonate is an effective and cheaper way to correct electrolyte concentrations in foals with mild abnormalities.

Older foals may be able to maintain hydration and correct mild electrolyte imbalances if free-choice water and electrolytes (in water or salt block with trace minerals) are provided.

If the foal is not interested in drinking, fluids and electrolytes may be administered via nasogastric tube.

Nutrition/caloric intake is very important in foals. Supplementation should be considered if the foal is not nursing or eating, of if the foal has evidence of proximal intestinal disease or lactose intolerance (idiopathic, rotavirus).

If the foal is interested in eating, controlled nursing is important as excessive milk intake may worsen the clinical signs. Excess of lactose in a dysfunctional small intestine may lead to bacterial breakdown of lactose to glucose and galactose. Glucose is osmotically active, drawing more water into the intestine. In addition, this increase in luminal glucose can lead to bacterial overgrowth.

If the foal is not interested in nursing, a small-bore feeding tube can be placed. These tubes have the advantage that the foal can nurse without problems, and they can be left in place for many days.

Bottle feeding should be done by experienced personnel as in some situations it may lead to aspiration pneumonia.

If there is no evidence of improvement and the foal does not tolerate enteral feeding, parenteral nutrition should be considered.

Antibiotics.

There are several factors to take into consideration in the selection of antimicrobial drugs, including current disease, aetiological agent, drug interactions, toxicity, and cost. The initial choice should be a broad-spectrum combination, unless the aetiological agent and sensitivity are known.

A combination of penicillin (or ampicillin) and an aminoglycoside (gentamicin or amikacin) is the most frequently used combination. It is important that the foal is well hydrated and that there is no evidence of renal disease, as aminoglycosides are nephrotoxic, particularly if there is dehydration and concurrent use of other nephrotoxic drugs (e.g. flunixin meglumine).

Third-generation cefalosporins such as ceftiofur (4.4–8.8 mg/kg IV BID), cefotaxime (40 mg/kg IV TID–QID), ceftazidime (40 mg/kg IV TID–QID), or ceftriaxone (10 mg/kg IV BID).

Metronidazole (20 mg/kg PO TID–QID) should be considered in foals with haemorrhagic diarrhoea, as this is a common finding in clostridial diarrhoea.

Anti-endotoxin therapy.

Flunixin meglumine (0.25 mg/kg IV TID) or polymyxin B (3000–6000 IU/kg IV BID, in 5% dextrose solution) should be considered in foals with severe sepsis or evidence of endotoxaemia.

Intestinal protectants. The use of these products is controversial, but protectants to consider are bismuth subsalicylate, kaolin, pectin, and activated charcoal. More recently, smectite-based products (Bio-Sponge) have been claimed to show good results in treating foal diarrhoea.

Non-steroidal anti-inflammatory agents.

Flunixin meglumine if there is evidence of endotoxaemia (0.25 mg/kg IV TID) or fever, pain, inflammation (0.25–1.1 mg/kg IV).

Ketoprofen (1.1–2.2 mg/kg IV) is a good choice in foals with fever and pain. It is less ulcerogenic than other non-steroidal drugs.

Plasma transfusion may be indicated in cases of FTPI or in foals with hypoproteinaemia.

Additional therapeutic measures.

Oral supplementation with lactase should be considered in foals with watery diarrhoea, foals with rotavirus infection, or in foals that do not tolerate enteral feeding. Anti-acid drugs such as cimetidine, ranitidine, or omeprazole can be used as foals are prone to developing gastric ulcers.