20 Buffer Therapy

335

From: Contemporary Cardiology: Cardiopulmonary Resuscitation Edited by: J. P. Ornato and M. A. Peberdy © Humana Press Inc., Totowa, NJ

20 Buffer Therapy

Martin von Planta, ^MD

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INTRODUCTION

The buffer therapy of acid–base changes during CPR is less controversial than in previous years. Overwhelming experimental and some clinical data failed to demonstrate an improvement in survival after buffer therapy. However, the scant data from random- ized controlled trials still impede a clear-cut recommendation on how really to treat cardiopulmonary resuscitation (CPR)-associated acid–base changes.

Conventional closed-chest CPR generates a cardiac output of approx 25% curtailing organ perfusion and oxygen delivery to the tissues. Anaerobiasis with rapid CO

genera- tion and slower accumulation of lactic acid results. Continuous CO

release from ischemic tissues, decreased CO

transport from the underperfused tissues to the lungs decreases alveolar CO

elimination accounting for the tissue CO

accumulation. Reduced ETCO

and hypercarbic venous and tissue acidemia and—under conditions of normal ventila- tion—hypocarbic arterial alkalemia ensue together with arterial and venous lactic aci- demia reflecting the “arterio-venous paradox.” The accumulation of tissue CO

results from local production of CO

, dissociation of endogenous bicarbonate when anaerobi- cally generated H

are buffered and reduced clearance of CO

as a result of reduced blood flow. In the heart, intramyocardial PCO

drastically increases with low coronary blood flow (Fig. 1).

Varying patterns of acid–base changes are related to the actual flow, the time windows of CPR and the cardiac arrest (CA) location. Arterial pH during well-performed CPR is usually normal, alcalotic (relative hyperventilation) and only late during CPR acidotic.

Acid–base changes during out-of-hospital CPR often present a combined metabolic and

respiratory acidemia. The triple low-perfusion acid–base abnormality makes the choice

of an optimal buffer agent difficult (Table 1). Protection of the airways, adequate venti-

lation and chest compression to restore oygenated blood flow are the first therapeutic

steps before any drug application may be evaluated. If CPR continues, various buffer

Fig. 1. Low-flow acidemia during CPR. Acid–base changes during CPR with mechanical chest compression and controlled ventilation in pigs. A triple acid–base defect is observed: venous and tissue hypercarbia, arterial hypocarbia, and arterial and venous lactacidemia. pH units; PCO₂ mmHg; lactate mmol/L. Based on refs. 22,24,83.

Table 1

Potential Buffer Substances for Use During CPR Anorganic buffers

Sodium bicarbonate (NaHCO₃) Sodium carbonate (Na₂CO₃) Organic buffers

THAM, tromethamine (CH₂OH₃ C-NH₂) Buffer mixtures

Carbicarb (Na₂CO₃ + NaHCO₃)

Tribonate (NaHCO₃ + Phosphate + THAM + Acetate)

agents are available of which sodium bicarbonate (NaHCO

) is the most widely used. To

date, very few randomized controlled trials are available and neither CO

-generating

(NaHCO

) nor CO

-consuming buffers (CARBICARB

, TRIBONATE

) were clini-

cally proven to increase return of spontaneous circulation (ROSC) or neurologically

intact long-term survival after CPR. In conclusion: the triple acid–base defect associated

with CPR is best corrected by restoration of the low-flow state.

PATHOPHYSIOLOGY OF ACID–BASE CHANGES Reduced Blood Flow and Acid–Base Changes During CPR

During the low-flow state of CPR only limited organ perfusion is maintained by external chest compression with cardiac output around 25% and reduced oxygen delivery to the tissues (1,2). The metabolism shifts from aerobic to anaerobic pathways with production of anaerobic metabolites such as lactic acid and CO

. Hence, a complex low- perfusion acid–base defect evolves that is only reversed after improvement of blood flow and restoration of adequate tissue oxygenation.

The reduced systemic and pulmonary blood flows curtail alveolar CO

elimination.

CO

release from the tissues after endogenous lactic acid buffering and decreased CO

transport from the underperfused tissues to the lungs results in reduced CO

elimination accounting for the accumulation of CO

in the prepulmonary venous vascular bed and in the tissues (Figs. 2 and 3).

Clinical studies demonstrated ETCO

decreases with venous and tissue hypercarbic acidosis and time coincident arterial hypocarbic alkalosis (3–7).

Predominantly, hypercarbia and lesser lactacidemia emerged as important acid–base derangements during CPR presenting a therapeutic dilemma. Acid–base changes are an additional epiphenomenon secondary to low flow and not a disease of its own. When cardiac output is reduced, tissue and venous hypercarbia is common. The magnitude of the arterio-venous pH and PCO

gradients clinically indicate the severity of the perfusion defect (8–13).

Systemic Acid–Base Changes

The highly diffusable CO

molecules rapidly cross the cell membranes into the cap- illaries increasing venous PCO

, thereby inducing hypercarbic venous acidemia. Part of this excess CO

is then removed during CPR by the small alveolar-capillary gas exchange.

The increased ventilation/perfusion ratio during adequate ventilation and decreased car- diac output explains the less acidotic arterial blood than venous blood, i.e., the arterio- venous paradox (3,14,15). Thus, early minor metabolic acidemia may be compensated by concurrent respiratory alkalemia because severe arterial acidemia is usually as a result of inadequate ventilation.

During adequate alveolar ventilation there is increased venous PCO

, decreased arte- rial PCO

, and time coincident decreased ETCO

(5,16,17). The arterio-venous gradients of pH, PCO

, and HCO

clinically increased for pH and PCO

but not for HCO

(3,5,9,18,19). Differing patterns of arterial acid–base derangements are usually related to the location of CA. Patients resuscitated in wards or in emergency departments had more severe arterial acidemia and hypercarbia than patients resuscitated in intensive care units. Thus, the acid–base changes of prolonged CA, such most out-of-hospital CPR cases, present a combined metabolic and respiratory acidemia (20).

Myocardial Acid–Base Changes and Coronary Perfusion

During myocardial ischemia of CPR anaerobic metabolism generates myocardial H

, CO

, and lactate with even greater pH and PCO

gradients in the coronary veins (21–23).

The intramyocardial CO

increases correlated with the coronary perfusion pressure dur-

ing experimental CPR when coronary blood flow was impaired (23,24).

Fig. 2. Pathophysiology of low-perfusion acid–base defect during CPR with restoration of blood flow.

The accumulation of CO

within the myocardium reflects the balance of local CO

production, dissociation of endogenous myocardial bicarbonate when buffering anaero- bically generated H

ions and reduced clearance of CO

as a result of low blood flow. CO

and lactic acid are the predominant determinants of intracellular pH during CPR. Extra- cellular HCO

, i.e., NaHCO

, exerts its effects on intracellular pH only after a delay as a result of low blood flow and prolonged transfer times from the blood into the intracel- lular compartment. Bicarbonate buffers anaerobically generated lactic acid increasing intracellular CO

and explaining the significant intramyocardial CO

increases.

Coronary perfusion pressure is the most important determinant of CPR successes cor-

relating with myocardial blood flow (25–27). Coronary perfusion pressures of 15 mmHg

in patients predicted outcome (28). When intramyocardial PCO

was above a value of 400 mmHg, coronary perfusion pressure was below 10 mmHg resulting in failure of experimental CPR (24).

Myocardial PCO

also correlates with the likelihood of successful recovery of heart function. Critical threshold levels of myocardial PCO

above 400 mmHg predicted failure of cardiac recovery after anoxic CA (23). In patients with aortic valve replace- ment, myocardial PCO

predicted the recovery of cardiac function (29,30). Thus, myo- cardial hypercarbia is a secondary acid–base derangement associated with reduced tissue perfusion.

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CO

is the major determinant of acidosis and decreases in HCO

seem to be of minor importance. In arterial and venous blood, HCO

remains almost unchanged during experimental CPR. In the myocardium, the HCO

was calculated by using the Hendersson-Hasselbach equation assuming the constancy of a pK value of 6.1 (31).

Only minor decreases of HCO

were documented, from 21 to 20 mEq/L after a tran- sient increase to 32 mEq/L during the first 5 minutes of CA (24).

Myocardial lactic acidosis is also evident during CPR with increased great cardiac vein lactate indicating either hypoxia or ischemia because lactate increases were con- sistently identified during myocardial ischemia in experimental animals and in humans (24,32).

Fig. 3. Normalized carbon dioxide and hemodynamic data during porcine CPR. Normalized PCO2

changes during CPR and mechanical chest compression and controlled ventilation in pigs. Drastic increases in intramyocardial PCO₂ are associated with lesser in the great cardiac vein and pulmo- nary artery and aortic PCO2 decreases. Decreased MAP and CPP are associated with myocardial CO₂ production.MYOPCO₂, intramyocardial PCO₂; GCVPCO₂, great cardiac vein PCO₂; PUAPCO₂, pulmonary artery PCO₂; ARTPCO₂, aortic PCO₂; MAP, mean aortic pressure; CPP, coronary perfusion pressure. (Based on refs. 22 and 24.)

Central Nervous System Acid–Base Changes

Brain tissue acid–base changes differ from those in the arterial or venous blood. The rapidly diffusable CO

molecules increase cerebrospinal hypercarbia during CPR (33).

This central hypercarbia may—when used with NaHCO

—contribute to the prolonged post-CPR cerebral depression observed in resuscitated patients (34). Cerebrospinal CO

increases after NaHCO

induced a “paradoxical” central nervous hypercarbia (35).

However, NaHCO

was not uniformly followed by intrathecal hypercarbia when NaHCO

was titrated during CPR or with worse outcomes especially when epinephrine was added (36). Continuous infusion of 1 mmol/kg NaHCO

during canine ventricular fibrillation (VF) and cardiopulmonary bypass was not associated with intracerebral acidosis deterio- ration (37).

The efficacy of CO

consuming buffers was not extensively studied. THAM improved during porcine lactic acidosis cerebrospinal acidemia, but NaHCO

failed to correct the intrathecal acid–base disturbances (38). CARBICARB

increased and NaHCO

further decreased intracerebral pH during lactic acidosis (39). 31P magnetic resonance studies demonstrated a paradoxical intracerebral acidosis after NaHCO

but not after CARBICARB

(40) and low dose CARBICARB

given during asphyxial CA reduced neurologic deficits in rats (41).

Acid–Base Changes, Buffer Agents, and Defibrillation

Conflicting reports resulted when acid–base changes and the effects of buffer agents on defibrillation were investigated. pH ranges from 7.03 to 7.71 were not associated with VF threshold changes or with special defibrillation difficulties during respiratory or metabolic acidosis and alkalosis. VF thresholds remained unchanged during respiratory alkalosis or acidosis (42–46). During metabolic acidosis a reduction in VF thresholds with increased incidence of VF was observed (47). Conversely, protective effects of respiratory alkalosis against VF were demonstrated (48). Only when metabolic acidosis was associated with hypoxia successful defibrillation was prevented (44,45,49). Buffer agents mostly failed to help defibrillation.

Hypercarbia and Survival

Myocardial PCO

is a determinant of cardiac resuscitability probably representing an epiphenomenon of reduced blood flow. Thus, intramyocardial hypercarbia is a secondary marker of reduced myocardial blood flow. However, experimental studies suggested that hypercarbia adversely affected outcome even when coronary perfusion pressure was maintained above the critical threshold for survival (50,51). During FiCO

ventilation concurrent arterial, venous and tissue CO

increases as a result of the rapid equilibrium of CO

across the membranes were observed. PCO

is selectively increased in the venous blood and in the tissues and in the arterial blood only very late in the CPR process.

Increased intramyocardial CO

levels induced myocardial “carbonarcosis” with decreased contractility accounting for the failure of successful CPR. In this setting, buffer agents may improve postCPR myocardial dysfunction (52).

TREATMENT WITH BUFFER AGENTS

The triple low-perfusion acid–base defect (venous hypercarbia, arterial hypocarbia,

and lactic acidemia) make the choice of any buffer agent a therapeutic dilemma. Para-

mount is the reduction of increased tissue CO

and the increase of tissue oxygenation

during reduced organ perfusion by adequate ventilation, chest compression, and early defibrillation (53–55). Potentially, anorganic, organic and buffer mixtures are available of which none were clinically proven to increase neurologically intact survival in patients (Tables 1–3).

Sodium Bicarbonate

NaHCO

dissociates to Na

and HCO

converting with H

to H

CO

and then to CO

and H

O, which are subsequently excreted by the lungs and kidneys. During normal ventilation and perfusion, the easily excretable CO

generated by NaHCO

is eliminated by the lungs effectively neutralizing excesses of H

making NaHCO

an efficient buffer:

H⁺ + HCO₃^–C H2CO₃C H2O + CO₂

Because the pK of the bicarbonate system is 6.1, HCO

should poorly buffer within the clinically relevant pH ranges. However, in 20 patients during CPR, the pK of carbonic acid was equivalent to that of healthy controls (31).

As the transport of CO

from the tissues to the lungs and its alveolar removal is impaired during CPR, NaHCO

may not act as efficient buffer (Figs. 2 and 3). NaHCO

induced paradoxical tissue and intracellular hypercarbic acidosis (56–58) and decreased myocardial contractility (58,59). Significant alkalemia is induced after NaHCO

(14,60) together with increased osmolal and sodium loads (14,61,62), and pediatric intracerebral hemorrhage (63,64). NaHCO

further induced left shifts of the oxyhemoglobin dissocia- tion curve decreasing P

(65,66). Most importantly is the failure of NaHCO

to improve defibrillation (14,25) or to increase neurologically intact long-term survival (60,67–72).

This may be as a result of simultaneous decreases in aortic diastolic pressure and in- creases in right atrial pressure resulting in decreases in coronary perfusion pressure (Table 4; 73).

Nevertheless, these findings are not unequivocal. Laboratory results vary widely as a result of experimental settings, timing and dosages of buffers, timing of blood sampling and perfusion magnitude after epinephrine. Better neurologic outcomes after 24 hours in dogs treated with NaHCO

and epinephrine were already demonstrated in 1968 (74). Con- versely, during porcine CPR the failure of NaHCO

to improve survival up to 20 minutes of untreated VF was confirmed (75). Recent experimental studies demonstrated after prolonged CAs improved outcomes when NaHCO

was used in conjunction with epi- nephrine (76–78). However, a multivariate regression analysis in 773 CA patients docu- mented a significant association between failed CPR and the use of NaHCO

as well as other ACLS drugs (79). Recently, a retrospective analysis of the timing of NaHCO

use of a previous randomized clinical trial demonstrated better ROSC in patients when no NaHCO

was administered during CPR (80). Indeed, the use of NaHCO

decreased in the 1990s after the publication of the 1986 American Heart Association (AHA) guidelines (81).

The magnitude of acid–base changes followed the dosage of NaHCO

used during CPR. With doses up to 1.5 mmol/kg, no changes in veno-arterial PCO

gradients were observed (60), with doses above of 2 mmol/kg, these gradients transiently increased (75).

Tissue pH—approximated by mixed venous pH—increased after NaHCO

(9,16,25,70,72)

and paradoxical intracellular pH decreases were observed after high doses of NaHCO

(35). With less NaHCO

this effect was not observed (70,82) and intramyocardial pH was

not reversed but continued to decrease after NaHCO

as after CARBICARB

and saline

placebo (83).

Table 2

Effects of Buffer Agents During Experimental and Human CPR

Author Year Main observations

Effects on survival

Telivuo 1968 No better survival after NaHCO3

Minuck 1977 THAM, NaHCO₃ and NaCl are equivalent during CPR Guerci 1986 NaHCO3 failed to improve survival

von Planta 1988 NaHCO₃, THAM and CARBICARB failed to improve survival Gazmuri 1990 NaHCO3 and CARBICARB failed to improve survival Roberts 1990 Significantly less surviving patients after NaHCO₃ Wiklund 1990 THAM and NaCl improve resuscitability, but not NaHCO3

Levy 1992 NaHCO₃ use in human CPR declined without decreases in survival Dybvik 1995 TRIBONATE^® failed to improve survival in humans

Bar-Joseph 1998 NaHCO₃ and CARBICARB^® promote ROSC Van Walraven 1998 NaHCO₃ in human CPR failed to improve survival

Leong 2001 NaHCO₃ may improve survival after prolonged arrest in dogs Effects on defibrillation

Turnbull 1966 pH of 7.14–7.60 without influence on fibrillation thresholds Gerst 1966 During metabolic acidosis more ventricular fibrillation Dong 1967 Respiratory alkalosis protects against ventricular fibrillation Yakaitis 1975 pH of 7.03–7.71 without influence on defibrillation

Kerber 1983 Metabolic or respiratory acid–base changes without influence on defibrillation of ventricular fibrillation

Cardiac effects

Reduction of coronary perfusion pressure (Arterial vasodilatation) Huseby 1981 Hyperosmolal solutions are arterial vasodilators von Planta 1988 THAM reduces coronary perfusion pressure

Kette 1991 Hyperosmolal solutions reduce coronary perfusion pressure Myocardial acidosis

Kette 1990 Intramyocardial acidosis not improved after NaHCO₃ or CARBICARB^® Myocardial contractility

Ng 1966 CO2 and NaHCO3 decrease and THAM increases contractility Clancy 1967 Na₂CO₃ increases and NaHCO₃ decreases contractility Cingolani 1970 Contractility depends on CO2, not on pH or HCO3–

Poole 1975 CO₂ decreases contractility in isolated rabbit myocardium Steenbergen 1977 CO2 decreases contractility in isolated rat myocardium

Graf 1985 Decreases in cardiac output and increases in lactate after NaHCO₃ Bersin 1988 NaHCO3 reduces and CARBICARB^® increases cardiac output Sun 1996 Buffers improve post-CPR myocardial dysfunction

Proarrhythmia

Lawson 1973 Alcalizinization increases ectopic arrhythmias

Douglas 1979 Bolus of NaHCO₃ induces ventricular fibrillation in pigs Effects on the CNS

CNS acidosis

Posner 1967 Paradoxical CNS acidosis after NaHCO3 during CPR Berenyi 1975 Severe hypercarbic acidosis in CNS liquor after NaHCO₃ Bureau 1980 NaHCO3 increases CNS liquor lactate

Table 2 (Continued)

Author Year Main observations

Wiklund 1985 THAM but not NaHCO₃ corrects liquor acidosis Kucera 1989 NaHCO₃ reduces intracellular pH, but not CARBICARB Rosenberg 1989 THAM and NaHCO₃ have equivalent effects on brain pH Katz 2002 CARBICARB^® reduces neurologic deficit

CNS damage

Posner 1967 Prolonged cerebral dysfunction after NaHCO₃ during CPR Thomas 1976 Severe intracranial bleeding after NaHCO₃

Huseby 1981 Bolus of NaHCO₃ increases intracranial pressure Metabolic effects

Alkalosis (Reduction of oxygen delivery, reduced P₅₀)

Douglas 1979 NaHCO₃ reduces arterial and venous oxygen concentration Bureau 1980 Reduction of oxygen delivery to the CNS after NaHCO₃ Bersin 1989 NaHCO₃ reduces P₅₀ in patients with heart failure CO₂ production

Case 1979 Myocardial CO₂ increases during ventricular fibrillation >400 mmHg Niemann 1984 50 mL 7.5% NaHCO₃ liberate 260–280 mmHg CO₂

Kette 1993 High intramyocardial CO₂ is associated with failure of CPR Hyperosmolality

Kravath 1970 NaHCO₃ induces acute hyperosmolality Ruiz 1979 Increased osmolality after NaHCO3

Hypernatremia

Mattar 1974 NaHCO3 induces severe hypernatremia and hyperosmolality Liver acidosis

Graf 1985 Reduction of intrahepatic pH and increase of CO2 after NaHCO3

Bersin 1988 NaHCO₃ increases intrahepatic acidosis more than CARBICARB^®

The impact of the coronary perfusion pressure on patient survival is well-known (28).

Especially after epinephrine, coronary perfusion pressure increased (84) and NaHCO

may be advantageous when combined with epinephrine (74).

Thus, restraint in the initial use of NaHCO

is advised during CPR (Table 5). NaHCO

should be abandoned for initial “conventional” CPR, it is not recommended for routine use in CPR! When arrest and CPR times are prolonged, NaHCO

in reduced dosages (0.5–1.0 mmol/kg iv bolus; half the dose thereafter) guided by actual bicarbonate con- centration or base excess may be used. With preexisting metabolic acidemia, hyperkale- mia, overdoses, or need to alkalize the urine, NaHCO3 may also be useful (53–55).

Carbicarb

(Na

CO

+ NaHCO

)

CARBICARB

is composed of equimolar amounts of NaHCO

and Na

CO

consum-

ing CO

(85). In dogs with hypoxic lactic acidosis, this buffer mixture normalized arterial

pH without increasing arterial CO

(58). In a porcine model of CPR, arterial and venous

PCO

decreased after CARBICARB

(70). Neither mean arterial pressure nor cardiac

index decreased after CARBICARB

but significant decreases in the coronary perfusion

pressure—attributed to a vasodilator effect of the hyperosmolal buffer mixture with an

increase in the right atrial pressure—were observed (70,73). Furthermore, CARBICARB

Table 3

Composition and Physico-Chemical Properties of Buffer Agents

Tribonate^® Bicarbonate Carbicarb^® NaHCO₃ + Na₂HPO₄ Substances and properties NaHCO₃ NaHCO₃ + Na₂CO₃ + THAM + Acetate

Na⁺, mmol/L 1000 1000

HCO₃^–, mmol/L 1000 333

CO₃ =, mmol/L 0 333

Osmolality, mOsmoL/L 2000 1667 750

pH of solution 8.0 9.6 8.1

Effect on CO_{2 B ? ?}

NaHCO₃, mmol/L 160

Disodium phosphate, mmol/L 20

THAM, tromethamine, mmol/L 300

Acetate, mmol/L 200

Tris-hydroxy-methyl-amino-methan (THAM):

Buffer capacity: 500 mmol/L

Table 4

Adverse Effects of Sodium Bicarbonate Alkalemia

Reduced tissue oxygen availability Increased risk of ventricular arrhythmias Hyperosmolality

Irreversible cerebral damage Arterial vasodilation

Decreased coronary perfusion pressure during CPR CO₂ production

Paradoxical intracellular acidosis Cerebrospinal fluid acidosis Decreased myocardial contractility Survival

Failure to facilitate defibrillation

No improvement of neurologically intact long-term survival

failed to reduce intramyocardial acidosis, myocardial CO

production, or to increase ROSC and long-term survival (83). Conversely, CARBICARB

decreased intrahepatic pH (58) and did not induce paradoxical intracellular acidosis in the rat brain (40). Hence, these limited data and the lack of controlled human experience do not advise the use of CARBICARB

as a potential buffer substance during CPR.

Tribonate (NaHCO

+ THAM + Phosphate + Acetate)

The buffer TRIBONATE

(TRIS) is a mixture of NaHCO

, THAM, phosphate and acetate which also consumes CO

is predominantly used in Scandinavia. A porcine CPR study demonstrated that TRIBONATE

exerted better intracellular alkalizing effects than NaHCO

, but survival was not better after TRIBONATE

than after NaCl (72).

In a prospective clinical trial, 245 TRIBONATE

-treated patients were compared with

257 saline placebo controls. Only 10% of the TRIBONATE

-treated patients but 14%

of the control patients were discharged alive. A logistic regression demonstrated that TRIBONATE

failed to improve survival (86). Thus, experimental and clinical data do not recommend the use of TRIBONATE

during CPR.

Adverse Effects of Buffers

Table 4 summarizes the adverse effects of NaHCO

. Excesses of buffers may trans- form acidosis into alkalosis. High pH levels decreased P

reducing tissue O

availability because increased hemoglobin affinity impaired tissue oxygen utilization (87). Thus, lactic acidosis may develop as a result of increased anaerobic glycolysis. Alkalemia also has proarrhythmic effects inducing ectopic dysrhythmias potentially triggering fatal ventricular arrhythmias (88).

Increased plasma osmolality above 350 mOsm/kg may induce permanent damage of white matter and intraventricular hemorrhage precluding return of normal brain function (61,89,90). Additionally, rapid osmolality increases are associated with hemodynami- cally relevant decreases of vascular resistance with transient but marked decreases in coronary perfusion pressures (73,91).

CO

stemming from NaHCO

paradoxically decreases intracellular and spinal fluid pH (34,35,57,92). In vitro myocardial contractility also decreased after NaHCO

(93).

However, these effects were not yet reported in intact animals or patients during CA. Few data documented an improved post-CPR myocardial function after buffer agents (52).

The most important shortcoming of the use of NaHCO

during CPR is its apparent failure to improve defibrillation success or to increase survival rates after CA. This may mostly be related to decreased oxygen availability, decreases in coronary perfusion pres- sure, or paradoxical acidosis when NaHCO

was administered as the only pharmacon.

Neither CO

-generating or CO

-consuming buffers were extensively tested in patients and their impact on ROSC or long-term survival after CA was yet never conclusively documented.

Table 5

Recommendations for NaHCO₃ Use During CPR

AHA European Resuscitation Council

Class I: with pre-existing hyperkalemia Consider NaHCO₃(50 ml of 8.4%) to correct Class IIa: with diabetic ketoacidosis, overdose severe metabolic acidosis. When blood gas

(tricyclics, cocaine, diphenhydramine) or need analysis is not available, consider NaHCO₃ to alkalize the urine. after 20–25 minutes of CA.

Class IIb: with prolonged resuscitation and effective ventilation; after ROSC and long arrest interval.

Class III: in hypercarbic acidosis (i.e., CPR without intubation).

Cave: Adequate ventilation and CPR as “major”

buffer agent.

NaHCO₃ dose: 0.5–1.0 mmol/kg.

Post-CPR Phase

During the initial minutes of ROSC, the acid–base abnormalities tend to normalize.

Sudden decreases in tissue and venous CO

accompany the normalization of tissue and venous pH. During the early phase of ROSC, ETCO

increases above normal levels. This

“overshoot” represents the washout of the retained CO

during CPR. Concurrently, arterial blood demonstrates a transient hypercarbia consistent with ETCO

increases. During con- tinued sufficient ventilation CO

normalizes within minutes and arterial pH remains low as a result of the persistence of increased lactate. The slower lactate uptake by the liver, kidney, myocardium, and gut account for the much slower return to normal in contrast to the more rapid decreases of CO

. Thus, little if at all buffer agents are needed during adequate perfusion and ventilation.

CONCLUSION

Given the fact, that few controlled clinical studies are available at this time, a balanced evaluation of experimental studies with NaHCO

demonstrated rather detrimental than beneficial effects regarding survival. CARBICARB

failed to mitigate intramyocardial acidosis and its hyperosmolal affected decreased coronary perfusion pressure. With TRIBONATE

, clinical data clearly demonstrated its failure. Thus, alternative buffer agents such as CARBICARB

or TRIBONATE

cannot be recommended for clinical use.

In CPR cases of short duration, adequate ventilation and efficient circulation elimi- nates generated CO

. The restoration of sufficient blood flow provides oxygen and coun- terbalances hypercarbic and metabolic acidemia by concurrent hypocarbic arterial alkalemia obviating the need for a buffer agent. However, during prolonged CPR, or in patients with preexisting hyperkalemia (class I), diabetic ketoacidosis, tricyclic, cocaine or diphenhydramine overdose (class IIa), NaHCO3 together with epinephrine may be indicated (NaHCO3: 0.5–1.0 mmol/kg; Table 5).

Alternative buffer agents such as CARBICARB

or TRIBONATE

cannot be rec- ommend for patient use because there are not enough clinical data available. A random- ized controlled trial examining and comparing CO

generating or consuming buffer agents during CPR is therefore mandated. Correction of the low-flow state remains the primary therapeutic goal. The correction of the acid–base equilibrium will then follow.

In general, efficient CPR is the best buffer therapy. The acidemia of CPR (arterial hypocarbia, venous and tissue hypercarbia and lactacidemia) is a symptom of low flow.

Thus, acid–base changes are a secondary phenomenon of CPR-associated low flow and not a pathophysiologic entity of their own. No randomized clinical trials with buffer agents documented improved ROSC or neurologically intact long-term outcome in patients.

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