Rational fluid therapy in camelid--a patient-based approach (Proceedings)

Old World Camelids are legendary in their ability to preserve water. Both the healthy camel and guanaco are able to sustain 25% body weight loss as a result of dehydration, without outward ill effects Unfortunately, these adaptations may also hamper the accurate identification of early hypovolemia in critically ill camelids by physical examination alone.

(a) Physical Examination

Tachycardia (heart rate > 90 beats per minute [bpm] in adults, > 120 bpm in crias) is a physiological defense against hypovolemia and aims to maintain cardiac output. Bradycardia in the face of significant volume depletion, however, may suggest advanced tissue damage and ensuing organ failure. On physical examination, poor peripheral perfusion in camelids may be indicated by cold extremities, a dull mentation and poor peripheral pulses or jugular fill.

The color and capillary refill of the patient's mucous membranes may vary according to the underlying disease. In the face of early, compensated septic or endotoxic shock, camelids may show hyperemic mucous membranes with a fast capillary refill time (CRT < 1 second) due to peripheral vasodilation and relative hypovolemia. Peripheral vasoconstriction on the other hand can manifest as tacky mucous membranes and prolonged CRT.

(b) Specific cardiovascular parameters

Most reported cardiovascular variables were established in healthy camelids undergoing anesthesia. For example, baseline systolic (153 – 152 mmHg), diastolic (106 – 119 mmHg) and mean (118 – 131 mmHg) arterial blood pressures were documented in 11 adult llamas anesthetized in lateral recumbency with low and high doses of Xylazine / Ketamine, respectively.

This study used an oscillometric device (Dinamap Veterinary Blood Pressure Monitor 8300) and neonatal size #4 or #5 cuff placed over the metacarpal artery of the nondependent limb.2 Invasive basal mean arterial blood pressures (MAP) of 152 mmHg were also reported in halothane anesthetized pregnant llamas, in contrast to a MAP of 47 mmHg in their fetal llamas crias at 70-90% of gestation. The fetal cardiac output was documented as 279 ml/kg/min with a systemic vascular resistance of 0.17 mmHg kg min ml-1.

Table 1: Normal CV parameters and peripheral oxygenation in standing, healthy adult alpacas4 Variable n Mean 95%CI CI (ml/kg/min) 7 110.3 (94.6−126.0) SAP (mmHg) 8 167 (150−183) DAP (mmHg) 8 96 (82−110) MAP (mmHg) 8 123 (112−135) mean PAP (mmHg) 8 14.4 (10.5–18.3) mean CVP (mmH2O) 8 6.8 (4.0–9.7)

CI – cardiac index ; SAP – systolic arterial pressure; DAP – diastolic arterial pressure; MAP – mean arterial pressure; PAP – pulmonary arterial pressure; CVP – central venous pressure

c) Central Venous Pressure (CVP)

Central Venous Pressure is utilized to estimate cardiac filling pressure or cardiac preload, as it approximates right atrial pressure. A low central venous pressure may be an indicator of insufficient circulating volume and the need for fluid therapy in humans. Normal CVPs in camelids have not been reported in the peer reviewed literature to date. However, a recent study documented a mean CVP of 6.8 mmH2O (95% CI: 4.0 – 9.7 mmH2O) in 14 standing, healthy, adult alpacas (mean weight: 62 ± 21kg, mean age: 4.5 yrs) that were outfitted with a Swan-Ganz pulmonary arterial catheter.

The CVP response to a fluid challenge is considered a more reliable indicator of volume status than the numerical value of central venous pressure alone. In humans, a CVP increase of < 1 mmHg in response to a bolus of 10ml/kg crystalloids or 2-3 ml/kg colloids is associated with hypovolemia, whereas an increase > 3 mmHg indicates probable fluid overload.7

However, comparable numbers have not been validated in camelids. Decreased ventricular distensibility (e.g. pericardial or pleural effusion) causes CVP values to be higher than expected at any given ventricular volume. Additionally, CVP measurements are prone to positional changes and thus require accurate catheter placement and consistent patient positioning. In camelids, CVP measurements are best obtained with the animal in sternal recumbency (cushed) and the neck extended. Measurements should be obtained at end expiration.

(d) Hematological and urinary parameters

Hypovolemia is expected to result in an elevated packed cell volume, hemoglobin concentration, plasma protein, blood urea nitrogen (BUN) and creatinine concentration over time. However, significant variations may occur based on the age of the patient and the type, duration and severity of underlying disease. These limitations also need to be considered when assessing blood chemistry values for sodium, chloride, potassium, pH and bicarbonate.

A combined evaluation a variety of laboratory variables is thus required to most accurately assess the degree of hypoperfusion and hypovolemia in critically ill llamas and alpacas. For example, hyperlactatemia is most commonly associated with tissue hypoxia related to hypoperfusion. Simplistically, lactate is an end-product of anaerobic metabolism. Although normal lactate values have not been established for camelids, a recent report documented a mean lactate of 0.6 mmol/L (95% CI: 0.54 – 0.62 mmol/L) in healthy adult alpacas (n=14) and 1.0 (95% CI: 0.88 – 1.2 mmol/L) in 2-7 day of neonatal crias (n=12), respectively.

Aside from volume depletion, hyperlactatemia may be seen in patients experiencing severe hypoxemia, anemia, cytokine inhibition of pyruvate dehydrogenase, hypermetabolic states (e.g. sepsis, SIRS), relative thiamine deficiency, decreased utilization or clearance of lactate by the liver (e.g. secondary to hypoperfusion) or increased production of lactate via inflammatory cells, shivering etc..

Azotemia alone is not a reliable indicator of hypovolemia in the immediate post partum period, as neonatal crias may show transiently elevated creatinine levels within the first 48 hrs after birth (spurious hypercreatinemia). Aside from volume depletion, perinatal azotemia may be attributed to maternal placental dysfunction (decreased creatinine clearance), perinatal asphyxia leading to fetal distress and ingestion of creatinine-rich fetal fluids, reduced renal clearance in premature neonates and less commonly congenital or acquired renal disease.

However, nursing neonatal crias often reduce serum creatinine levels below 1.5 mg/dL within 2-3 days post partum, based on the author's observations. The neonate's physiologically low creatinine may be associated with the low muscle mass and high fluid ingestion of nursing animals. The assessment of trend changes in creatinine concentration is considered a superior diagnostic tool, compared to the evaluation of absolute values in individual patients. In general, normal urine production can be used to estimate that cardiac output and vasomotor tone are normal.

The rate of urine production in camelids is lower than in many other species, and may vary according to diet. In 1995, Lackey et al reported normal indices of renal function in 12 healthy male adult llamas fed a mixed alfalfa/grass or pure grass hay diet. The total urine volume per day for llamas fed mixed hay ranged from 628 to 1,760 ml (median: 1,308 ml urine per day; +/-0.3ml/kg/hr), compared with a daily range of 620 to 1,380 ml (median: 928 ml urine per day) for llamas fed grass hay. Median urine osmolality was higher in llamas fed mixed hay (1,906 mOsm/kg of body weight), compared with llamas fed grass hay (1,666 mOsm/kg). Creatinine clearance did not vary significantly over time for either diet.

Fluid distribution and requirements of the “healthy camelid”

Fluid imbalance ensues when fluid demands or losses (insensible, renal and gastrointestinal) exceed fluid intake. Inadequate nursing (crias), central depression, hypoosmolarity (reduced thirst drive), pain, stress or vomiting may reduce fluid intake and contribute to hypovolemia. However, absolute hypovolemia is most commonly associated with gastro-intestinal fluid loss in camelids (diarrhea, vomiting, intestinal fluid sequestration), while relative hypovolemia is induced by states of vasodilation (sepsis, SIRS [systemic inflammatory response syndrome] or endotoxemia).

Most disease states drastically alter reported “normal” homeostatic mechanisms and fluid distribution. Additionally, each individual patient, irrespective of species, will develop varying degrees of physiological derangements during critical illness. For this reason, current recommendations advocate the use of physiological parameters as clinically relevant endpoints of resuscitation in many mammalian species.

Intravenous goal-directed fluid therapy

Human studies have shown that a more definitive resuscitation strategy involves goal-oriented manipulation of cardiac preload (circulating volume), afterload (peripheral resistance), and cardiac contractility to achieve a balance between systemic oxygen delivery and oxygen demand. This type of “early goal-directed therapy” is a cardiovascular support protocol aimed at early hemodynamic optimization, which has been empirically applied to “critically ill” llamas and alpacas at the author's clinic.

The protocol is initiated as soon as clinically significant hypoperfusion is identified upon admission and targets extrapolated end points of resuscitation. The target variables are derived from hemodynamic monitoring as previously reported and include central venous pressure [CVP], mean arterial pressure [MAP], lactate concentration, pH, and central venous oxygen saturation [Scvo2] as a surrogate of the oxygen supply/demand balance.

The human literature strongly supports that resuscitation should start as early as possible to prevent further organ dysfunction and failure.13 The longer the resuscitation is delayed, the less likely a beneficial effect will be achieved.14 In short, the resuscitation strategies designed to improve tissue oxygenation are unlikely to be helpful once cellular dysfunction and death have evolved. Human guidelines have suggested that treatment goals during the first 6 hrs of resuscitation should include all of the following: CVP of 8–12 mmHg, MAP ≥ 65 mmHg, urine output of ≥ 0.5 mL/kg/hr, and a central venous oxygen saturation (Scvo2) of ≥70%.

How well these parameters can be adapted to camelids, remains speculative. Urine output may be the most technically challenging parameter to monitor in this species and is commonly (even if crudely) evaluated via determination of voiding frequency rather than exact assessment of urine quantity. Lack of observed urination (< 3 times a day in adults and < 5 times a day in neonates) in intermittently, but closely monitored animals may be a good indicator of inadequate end-organ (renal) perfusion. In general, the clinical application of early goal-directed therapy in critically ill llamas and alpacas at the author's teaching hospital has significantly enhanced the understanding, monitoring and safety of fluid therapy in this species. Extrapolated parameters that we aim to restore and maintain in camelids, commonly include the following:

·         CVP of 4–6 mmHg

·         MAP ≥ 65 mmHg or normalized pulse quality

·         “Regularly” observed urination (> 3 times per day in adults, > 5 times in neonates)

·         Scvo2 ≥ 70%

·         Lactate < 2 mmol/l

·         Colloid oncotic pressure (COP) > 12 mmHg or total protein > 5 g/dl

Nonetheless, it should be noted that these parameters have only been used empirically over the past 5 years at a single referral clinic and thus merely serve as a guideline in the individual patient management.

Although continuous rate infusion is generally preferred once basic volume deficits are replaced, initial fluid therapy in significantly hypovolemic camelids commonly includes 20 ml/kg fluid boluses over 15 – 30 minutes, predominantly guided by trend changes in central venous pressures (CVPs).

Fluid therapy in camelids with respiratory illness

Adequate gas exchange not only depends on alveolar ventilation, but also on perfusion and diffusion capacity. Preservation of pulmonary and systemic perfusion is thus essential in the treatment of compromised camelids (especially neonates).  However, a protocol of conservative fluid management is often indicated in the treatment of camelids with lung dysfunction, especially those related to immaturity and pulmonary inflammation (e.g. septic pneumonia, acute lung injury) to counteract edema formation. This balance is best achieved by the principles of goal directed fluid therapy.

However, the central venous pressure (CVP) targets should be lowered to 2-4 mmH2O in camelids with pulmonary inflammation, as long as urine production and end organ perfusion is preserved. Conservative colloid administration may be superior to crystalloid therapy in this patient group, especially in the face of hypoproteinemia. It has been stated that even modest decreases in pulmonary vascular pressure can reduce pulmonary edema in patients with acute lung injury.

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