Morbidity & Mortality Conference

Feb 17, 2011

54
1

10 1

2-3 30 20

Physical examination

GA : Thin middle age man, thin, E1VtM4 Vital signs : BP 70/40 mmHg, PR 110/min RR 24/min BT 36.8 c HEENT : Pale, no jaundice, parotid gland enlargement both side No spider nevi, no gynecomastia Lung - clear, equal both side Heart - regular pulse, normal S1S2, no murmur, no heave, no thrill Abdomen : distention, liver and spleen not palpable, no fluid thrill Ext. - no pitting edema PR : melena 1 L in diaper, NG tube : Fresh blood per NG

Lab 9.00 6/2/54

CBC : WBC 19,810 Hb 14.1, Hct 39.4 MCV 96, MCH 34.4 MCHC 35.8 Plt. 68,000
RDW 12.9

PMN 74, Band 17, Lymp 6, Mono 3 PTT 27.7 (control 25.5), PT 15.8 (control 11.5)
INR 1.40

BUN 46.0, Cr 2.84 Na 129 K 3.82 Cl 76.2

T-CO2 10.8

Initial ABG
11.09 . pH 7.32 PCO2 14 PO2 116 HCO3 12 SaO2 98% 12.12 . pH 7.10 PCO2 28 PO2 30 HCO3 12 SaO2 39.1%

Problem lists
Massive UGIB with hemorrhagic shock Alteration of consciousness Chronic alcoholism suspected chronic liver
disease

AKI with metabolic acidosis with mixed

respiratory alkalosis

Hyponatremia

EGDscopy
Severe reflux esophagitis LA class D, no EV,
mild PHG without subepithelial hemorrhage

No gastric varices Deulafuoys lesion with arterial spurting at high

lesser curve

Rx : adrenaline injection (1:10000) 40 ml +

bipolar + hemoclips x 2 + APC at raw surface bleeding was stopped

MAP around 55-65 mmHg during procedure

 acidemia level and Threshold for bicarb

Threshold for bicarbonate therapy

What blood pH do you choose to begin

therapy ?

A. pH < 7.3 B. pH < 7.2 C. pH < 7.1 D. pH < 7.0

7/2/54 6/2/54 Hypovolemic shock

EGDscopy
ABG 14.10 pH 7.24 PCO2 8.7 PO2 152 HCO3 9.0 ABG 16.45 pH 7.25 PCO2 16.4 PO2 205 HCO3 11.2 Lab 23.24 Na+ 143.9 K+ 3.35 Cl- 98.2 T-CO2 13.7

ABG 19.00 pH 7.293 PCO2 19.2 PO2 100 HCO3 13

7/2/54 6.30 . 10

BP drop MAP 50-60 14.25 7.5%NaHCO3 1 amp in 1 hr from ER 7.5%NaHCO3 1 amp then 1 amp V in 1 hr 17.00 . 7.5% NaHCO3 1 amp IV

BP stable

7/2/54 8.30 . 2

Cause and investigation ?

7/2/54 6/2/54 Hypovolemic shock

EGDscopy
ABG 14.10 pH 7.24 PCO2 8.7 PO2 152 HCO3 9.0 ABG 16.45 pH 7.25 PCO2 16.4 PO2 205 HCO3 11.2 Lab 23.24 Na+ 143.9 K+ 3.35 Cl- 98.2 T-CO2 13.7 ABG 5.30 pH 7.575 PCO2 24.7 PO2 60.4 HCO3 28.6 7/2/54 6.30 . 10 ABG 13.23 pH 7.604 PCO2 26.8 PO2 77.8 HCO3 30

ABG 19.00 pH 7.293 PCO2 19.2 PO2 100 HCO3 13

BP drop MAP 50-60 14.25 7.5%NaHCO3 1 amp in 1 hr from ER 7.5%NaHCO3 1 amp then 1 amp V in 1 hr 17.00 . 7.5% NaHCO3 1 amp IV

BP stable

7/2/54 8.30 . 2

7/2/54 6.29 . BUN 45.2 Cr 2.12 Na 149 K 2.90 Cl 103.4 T-CO2 22.7 DB 4.28 TB 4.71 AST 4710 ALT 685 ALP 50 TP 5.0 Alb 2.7 Ca 5.7 Magnesium 11.52 mg/L (16-26) Phos 0.5 Amylase 697 (28-100 U/L) Lipase 2686 (0-60 U/L)

Problem lists bleeding with UGIB with Deulafuoys

hemorrhagic shock

Massive blood transfusion (PRC 7 u, FFP 2000

ml, PC12 u)

Metabolic acidosis Alteration of consciousness New onset seizure Acute kidney injury Acute pancreatitis Hypocalcemia Hypophosphatemia Hypomagnesemia

 Metabolic acidosis Effects Cause - potential bicarb Treatment Threshold for bicarbonate therapy

Causes : Metabolic acidosis

Organic acid Non-organic acid
# Loss of base - GI loss # RTAs # Hypoaldosteronism

Effect of metabolic acidosis

pH < 7.00 - 7.20

Sodium bicarbonate in cardiac arrest : a reappraisal. Am J Emerg Med 1996.

Overcorrection

Sodium bicarbonate in cardiac arrest : a reappraisal. Am J Emerg Med 1996.

Excess CO2, freely diffuse into myocardial and cerebral Extracellular alkalosis cell shift O2 dissociation curve to Lt. causing intracellular Hypoxia acidosis Exacerbate Central venous acidosis Inactivate catecholamines

BICARBONA TE THERAPY
Hypernatremia Hyperosmolarity

Compromise CPP (decreased systemic vascular resistance)

Causes
Organic acid Non-organic acid
# Loss of base - GI loss # RTAs # Hypoaldosteronism

In both lactic and ketoacidosis, unmeasured

anion is important physiologically

Correction of underlying abnormality results in

metabolism of excess anion, which regenerates at least some of bicarbonate that was lost during initial buffer system

This usually occurs as a consequence of an increase in ammonium excretion. 2. Liver: Hepatic metabolism of acid anions to produce bicarbonate The normal liver has a large capacity to metabolise many organic acid anions (eg lactate, ketoanions) with the result that bicarbonate is regenerated in the liver. - In severe ketoacidosis there is often a large loss of ketoanions due to the hyperglycaemia induced osmotic diuresis. - This leaves a shortfall of ketoanions to be used to regenerate bicarbonate as a consequence of their metabolism in the kidney. 3. Exogenous Administration of sodium bicarbonate - This is the time honoured method to 'speed up' the return of bicarbonate levels to normal. - Indeed, this may be useful in mineral acidosis (hyperchloraemic metabolic acidosis) where there are no endogenous acid anions which can be metabolised by the liver. - However, in most other cases of metabolic acidosis this administration is either not helpful or may be disadvantageous.

Source of bicarbonate 1. Kidney: Renal generation of new bicarbonate

Special situation
Lactic acidosis Diabetic ketoacidosis Cardiac arrest

Bicarbonate and lactic acidosis

Questions
Is low pH bad ? Can sodium bicarbonate raise pH in
vivo ?

Does increasing the blood pH with

sodium bicarbonate have any salutary effect ?

Does sodium bicarb have negative side

effects ?

Lactic acidosis
Sodium bicarbonate is clearly effective in raising
arterial pH in critically ill patients with lactic acidosis

Impact on intracellular pH is unknown but it is

negative in animal studies

Despite the correction of acidemia, sodium

bicarbonate has no cardiovascular effect

Lactic acidosis
We believe most clinicians who continue to use
bicarbonate for patient with lactic acidosis do so largely because their inclination to action

How can I fail to use bicarbonate when no

alternative therapy is available and mortality rate of this condition is so high ?

Lactic acidosis
Given the lack of evidence supporting its use,
we cannot condone bicarbonate administration for patients with lactic acidosis

We extend this to those with pH < 7.2 on

vasoactive drugs, inasmuch as bicarbonate has no measurable beneficial effects even in these sickest patients

Indeed we do not give or advise bicarbonate

infusion regardless of the pH

2009

- Use of bicarbonate in DKA is controversial - Prospective randomized study in 21 patients failed to show either beneficial or deleterious changes in morbidity or mortality with bicarbonate therapy in DKA with pH 6.9-7.1 - 9 small studies in total 434 patients with DKA (217 treated with bicarbonate and 178 patient without alkali therapy), bicarbonate offers no advantage in improving cardiac or neurologic functions or rate of recovery of hyperglycemia and ketoacidosis - Several deleterious effects : increased risk of hypokalemia, decreased tissue O2 uptake, cerebral edema and paradoxical CNS acidosis No prospective randomized studies concerning the use of bicarbonate in DKA with pH < 6.9 have been reported - Recommended adult patient with pH < 6.9 should receive 100 mmol sodium bicarbonate in 400 ml sterile water with 20 mEq KCL administered at rate of 200 ml/hr for 2 hr until venous pH > 7.0

In ketoacidosis, substantial amounts of acetoacetate and hydroxybutyrate are lost in the urine before the patient arrives at the hospital. Thus, not only has the patient converted bicarbonate to potential bicarbonate, he is truly bicarbonate deficient. More urinary loss of ketone bodies occurs after fluid administration and volume repletion. Hence, the ubiquitous hyperchloremic metabolic acidosis we see the day after insulin therapy is initiated. In ketoacidosis, it is almost never necessary to give bicarbonate even though the patient is bicarbonate deficient unless renal function is permanently impaired. Therapy with fluids and electrolytes restores extracellular volume and renal blood flow, thus enhancing the renal excretion of acid and regenerating bicarbonate. Okuda et al.18 demonstrated in humans with diabetic ketoacidosis, as well as in the in situ acidemic perfused rat liver (pH of 7.15), that bicarbonate therapy markedly increased blood acetoacetate and hydroxybutyrate levels. Infusion also increased blood lactate levels approximately three-fold. Others have reported similar findings.19 Indeed, bicarbonate therapy actually delays the removal of ketone bodies from the blood.

2 studies Other studies Increased ROSC - no benefit or poor outcome Increased hospital admission Increased survival to hospital d/c Some special resuscitation situation - Pre-existing metabolic acidosis - Hyperkalemia - TCA overdose

Not recommend for routine use in cardiac arrest (Class III, LOEB)

46 Intensivists, 53 Nephrologists Usually in North america and Canada

28% 86% 67% 60%

Lactic acidosis

Ketoacidosis

1. Ventilation must be adequate to eliminate the CO2 produced from bicarbonate

Bicarbonate decreases H+ by reacting with it to to produce CO2 and water. For this reaction to continue the product (CO2) must be removed. So bicarbonate therapy can increase extracellular pH only if ventilation is adequate to remove the CO2. Indeed if hypercapnia occurs then as CO2 crosses cell membranes easily, intracellular pH may decrease even further with further deterioration of cellular function.

2. Bicarbonate may cause clinical deterioration if tissue hypoxia is present

If tissue hypoxia is present, then the use of bicarbonate may be particularly disadvantageous due to increased lactate production (removal of acidotic inhibition of glycolysis) and the impairment of tissue oxygen unloading (left shift of ODC due increased pH). This means that with lactic acidosis or cardiac arrest then bicarbonate therapy may be dangerous.

3. Bicarbonate is probably not useful in most cases of high anion gap acidosis
Lactic acidosis can get worse if bicarbonate is given. Clinical studies have shown no benefit from bicarbonate in diabetic ketoacidosis. In these cases, the only indication for
bicarbonate use is for the emergency management of severe hyperkalaemia.

4. The preferred management of metabolic acidosis is to correct the primary cause and to use specific treatment for any potentially dangerous complications
The organic acid anions serve as bicarbonate precursors to regenerate new bicarbonate once the primary cause is treated. In some forms of acidosis specific treatment to prevent problems is possible (eg ethanol blocking therapy in ethylene glycol poisoning.) If hyperkalaemia is present then [K+] can be decreased by bicarbonate therapy. Also, bicarbonate therapy can cause an alkaline diuresis which hastens renal salicylate excretion.

5. Bicarbonate therapy may be useful for correction of acidaemia due to non-organic (or mineral) acidosis (ie normal anion gap acidosis)
In non-organic acidosis, there is no organic anion which can be metabolised to regenerate bicarbonate. Once the primary cause is corrected, resolution of the acidaemia occurs more rapidly if bicarbonate therapy is used. Amounts sufficient for only partial correction of the disorder should be given. The aim is to increase arterial pH to above 7.2 to minimise adverse effects of the acidaemia and to avoid the adverse effects of bicarbonate therapy. If the patient is improving without serious clinical problems then waiting (f

Indication : Bicarbonate therapy

Bicarbonate therapy : pH 6.9-7.0 Calculation for bicarbonate deficit ABG q 1-2 hr

Bicarbonate treatment in Metabolic acidosis

1. Ventilation must be adequate to eliminate the CO2 produced from bicarbonate 2. Bicarbonate may cause clinical deterioration if tissue hypoxia is present (Lt shift of curve and acidotic inhibition of glycolysis) 3. Bicarbonate is probably not useful in most cases of high anion gap acidosis 4. Correct the primary cause and to use specific treatment for any potentially dangerous complications 5. Bicarbonate therapy may be useful for correction of acidemia due to non-organic (or mineral) acidosis (ie normal anion gap acidosis)

Reduce risk of iatrogenically induced alkalosis

Calculation of base deficit Not attempt to complete correction of

base deficit

Initial dose : 1 mEq/kg Close follow up Alternative : Non-CO2 generating buffer

ex. Carbicarb, THAM

Calculation of bicarbonate therapy

Treatment

Treatment of underlying causes

Goal of therapy in metabolic acidosis is restoration of a normal extracellular pH. Normal renal response to metabolic acidosis is to markedly increase acid excretion, primarily as ammonium. Exogenous alkali may not be required if the acidemia is not severe (arterial pH >7.20), the patient is asymptomatic, and the underlying process, such as diarrhea, can be controlled.

With more severe acidemia, correction can be achieved more rapidly by the administration of sodium bicarbonate. Initial aim of therapy in most patients is to raise the systemic pH above 7.20 Some uncertainty about the absolute benefits of achieving this level, particularly in patients with diabetic ketoacidosis and lactic acidosis . Treatment of the underlying disorder will permit metabolism of the organic anion, which regenerates most or all of bicarbonate lost in the initial buffering process.

Bicarbonate therapy is generally not given unless the arterial pH is below 7.00 in ketoacidosis or 7.10 to 7.15 in lactic acidosis.

Calculation of bicarconate deficit

Assuming that respiratory function is normal, attainment of a pH of 7.20 usually requires raising the serum bicarbonate to 10 to 12 meq/L HCO3 deficit = HCO3 space x HCO3 deficit per liter

The apparent bicarbonate space is a reflection of total body buffering capacity, which includes extracellular bicarbonate, intracellular proteins, and bone carbonate At a normal to moderately reduced serum bicarbonate concentration, excess hydrogen ions are buffered proportionately through the total body water and the apparent bicarbonate space is approximately 55 percent of lean body weight.

Bicarbonate space rises in severe metabolic acidosis, since the fall in the serum bicarbonate concentration means that there is an ever increasing contribution from the cells and bone, which have a virtually limitless supply of buffer. Bicarbonate space can reach 70 percent when the serum bicarbonate concentration falls below 10 meq/L and may exceed 100 percent at levels below 5 meq/L

Calculation of bicarconate deficit

deficit per liter = HCO3 space HCO3 deficit (2.6 [HCO3])] x BW[0.4kg) Bicarbonate space = (in +

x HCO3

Ex. BW 60 kg, serum bicarbonate 6 mEq/L, initial aim = 12 meq/L The bicarbonate space is approximately 80 percent and 60 percent of body weight, respectively, at these two concentrations Taking an average value of 70 percent: Bicarbonate deficit = 0.7 x 60 x (12 6) = 252 meq

Calculated deficit does not account for ongoing losses.

 Hypocalcemia Acute pancreatitis Alcohol withdrawal

Hypocalcemia

Setting

hypocalcemia

1. High index of suspicious Predisposing conditions 2. Specific signs - Chvosteks sign - Trousseaus sign - ECG

Chvosteks sign
Positive in 25% of healthy individual Negative in 29% of laboratoryconfirmed hypocalcemic patient

Trousseaus sign
Positive in 1% of healthy individuals Positive in 94% of confirmed hypocalcemic patient

Prolong QT

Alcohol related seizure

Alcohol-related seizures All seizures in the aggregate associated with alcohol use, including the subset of AWS

Alcohol withdrawal seizure

Victor and Brausch, Epilepsia 1967 241 Alcohol abusers with seizures or alcohol-related illness complicated by seizures

# Adult onset # Alcoholic for many years # Can occur in minor alcohol withdrawal, major alcohol withdrawal or delirium tremens # Onset 6-48 hrs after cessation of drinking 90% had 1-6 GTC seizures, without warning 60% experienced multiple seizures, usually 2-4 within 6 hrs (recent much lower rate of repeat seizure 13-24%)

Alcohol related seizure : mechanism

Summary points
Metabolic acidosis and bicarbonate therapy Condition, threshold, monitoringH Hypocalcemia recognition Alcohol related seizure, several causes to
think of.

THANK YOU