Shortness of breath – a symptom not always understood ❧ Case Conference March 18, 2014 Andrea Caballero Chief Complaint ❧ ❧ DOE x 1 week HPI – 1st presentation ❧ 54 year-old woman with PMHx of HIV (CD4 count 485; 30.6%), DM2, HTN and CKD stage 3 who presented with DOE. Four days prior to presentation, she experienced an episode of SOB while walking in the Dollar Store. She returned to her car and sat down for a while and her SOB resolved. Dyspnea progressively worsened => exacerbated with exertion and improved with rest. ❧ No CP, diaphoresis, headache, dizziness, N/V ❧ At baseline she could ambulate a little over a block before getting SOB. On presentation she would get SOB after 50ft. ❧ Baseline 3 pillow orthopnea; no PND ❧ Decreased PO intake, but still urinating 5-6 times/day due to the furosemide she takes for pedal edema (at baseline). ❧ No fever, chills, cough or calf pain/redness/swelling. HPI ❧ ❧ Earlier that day: ❧ Pt was seen at diabetes clinic and metformin was discontinued due to increase in Creatinine from baseline of 1-1.4 (GFR 50-59) to 2.6 (GFR<30). ❧ Patient did not complain of any symptoms Past Medical History ❧ ❧ HIV (diagnosed on 3/2013– CD4 391 / 24.3% and on 7/13- 485 / 30.6%). ❧ Hypertension ❧ Diabetes mellitus type 2 (A1C 7.8 on day of admit) ❧ CKD stage 3 ❧ Dyslipidemia ❧ Iron Deficiency Anemia ❧ Vitamin D deficiency ❧ Central Retinal Vein Occlusion with Cystoid Macular Edema Past Surgical History ❧ ❧ Cone biopsy ❧ Hysteroscopy w/ polypectomy Medications ❧ ❧ Lamivudine-Zidovudine ❧ Furosemide 40mg Qday 150-300mg BID ❧ Spironolactone 50mg Qday ❧ Raltegravir 400mg BID ❧ Pravastatin 40mg QHS ❧ Metformin 1000mg BID ❧ Esomeprazole 40mg Qday ❧ Insulin Glargine 42Units BID ❧ Colace 100mg prn ❧ Insulin Aspart 16Units QAC constipation ❧ Amlodipine 10mg Qday ❧ Ferrous Gluconate 240mg ❧ Clonidine 0.2 TID Qday ❧ Labetalol 300mg TID ❧ Loratidine 10mg Qday ❧ Lisinopril 40mg Qday ❧ Timolol 0.5% opth BID Allergies ❧ ❧ NKDA Family History ❧ ❧ DM2 and HTN in several first degree relatives Social History ❧ ❧ Negative for tobacco, alcohol, and illicit drug use ❧ Lives alone and works as a bus driver and hall monitor at a school in the lower 9th ward ❧ 3 heterosexual partners; partner 9 months prior to HIV diagnosis likely source Health Maintenance ❧ ❧ Up to date on influenza vaccine ❧ Up to date on Tdap vaccine ❧ Received 1st dose of Hepatitis B vaccine ❧ No pneumococcal vaccine ❧ Up to date on PAP ❧ Mammogram > 1yr ❧ Colorectal cancer screen - FOBT neg x 3 ROS ❧ ❧ Gen: No weight changes ❧ HEENT: no visual changes/sore throat/rhinorrhea ❧ CV: per HPI ❧ RESP: per HPI ❧ GI: per HPI ❧ Neuro: No numbness ❧ Skin: No new rashes ❧ GU: No complaints Physical Exam ❧ ❧Vitals ❧Triage ❧ BP 111/59 P 107 RR 26 T 96.8 O2 100% on RA ❧ 5’0” 126kg BMI 54 ❧Exam ❧ BP 93/57 P 94 RR 16 T 98.8 O2 98% on RA Physical Exam ❧ ❧ Gen: Alert, appears stated age and cooperative, obese, uncomfortable but in no distress. Could speak in full sentences ❧ Head: Normocephalic, without obvious abnormality, atraumatic ❧ Eyes: Conjunctivae/corneas clear. PERRL, EOM intact. ❧ Throat: Lips, mucosa, and tongue normal; teeth and gums normal ❧ Neck: No adenopathy, no carotid bruit, unable to assess JVD secondary to body habitus, supple, symmetrical, trachea midline ❧ Lungs: Clear to auscultation bilaterally, no w/r/c ❧ Heart: Tachycardic, regular rhythm, S1, S2 normal, no S3/S4/m/r ❧ Abdomen: Obese; bowel sounds normal; soft, non-tender; no organomegaly could be appreciated Physical Exam ❧ ❧ Extremities: Extremities normal, atraumatic; no cyanosis or edema ❧ Pulses: 2+, symmetric radial and DP pulses bilaterally. ❧ Skin: Dry skin, no rashes ❧ Neuro: Awake, alert, and oriented x4. Sensation intact to light touch; biceps, patellar reflexes 2+. Strength is 5/5 bilaterally in the upper and lower extremities. Cerebellar function intact as demonstrated by finger to nose evaluation. CN II-XII: intact Labs Admit ❧ (7-25) (20-25) (13.5-17.5) 135 101 48 204 (10-11) (80-100) 5 17 2.66 (65-99) 10 113.5 (25-28) (1.2) (5-6) 6.8 234 (24-32) (0.5-1.10) (4.5-11) 30.3 17.2 (33-34) (11.5-14.5) AG 19 (40-51) Ca 9.1 Mg 2.1 Phos 3 N 60 L 21 M 16 E 3 TP Alb TB AST ALT ALP 7.4 3.2 1.0 35 29 114 (3.4-5) Labs cont’d ❧

UA: Sg 1.020 RBC 6-10 Trop <0.01 pH 5.0 WBC 3-5 BNP 29 Prot Neg Sq >100 D-dimer 2519 Glu Nml Bact Rare Lactic acid 4.4 (0.3-2.4) Ket 5 Casts Neg CK 460 Blood 25 PT 12.5/NR 1.2/PTT 27 Nitrite Neg ABG on RA 7.25/35/80/94.4% Urobil 1.0 Utox - negative (7.35-7.45)(35-45) Hospital Course ❧ ❧ DOE - negative trop, BNP 29. CXR clear. D-dimer 2519, VQ scan negative. TTE with normal systolic function (EF >55%). ABG 7.25/35/80/15. Believed to be partly 2/2 body habitus. ❧ AGMA - thought to be 2/2 metformin and ART. Both discontinued. Lactic acid 4.4 on admit, 4.3 on discharge. AG improved (15) 138 107 35 204 5.2 18 1.5

❧ AKI on CKD3 - FeNa 0.25%, no eos. CK 460. Creatinine decreased to 1.5 by discharge with IVF. Thought to be from dehydration and over diuresis. Stopped ACEI, spironolactone and furosemide. Hospital Course cont’d ❧ ❧ HIV - ART stopped. CD4 432 (27.2%) ❧ DM2 - A1C 7.8. Basal insulin decreased to 25 Units BID

❧ Patient was discharged home and followed up with her PCP at HOP 3 days later. HPI – 2nd presentation ❧ ❧ Re-presented to ED 5 days after discharge stating that her DOE was not improved ❧ Since the time of discharge she had also been experiencing lower abdominal pain (unable to point to exact location), present all the time, 10/10. She was not able to keep any food or liquids down, despite feeling hungry. She would vomit whenever she attempted to eat or drink anything. ❧ Non-bloody, non-bilious, usually whatever food/drink she had just consumed. ❧ No alleviating factors. ❧ Denied subjective fevers, chills, night sweats, dysphagia, changes in BM quality/color (last BM morning of presentation), dysuria/hematuria, discharge. Physical Exam ❧ ❧Vitals ❧Triage ❧ BP 136/73 P 98 RR 24 T 97.8 O2 99% on RA ❧ 5’0” 126kg BMI 54 ❧Exam ❧ BP 111/47 P 99 RR 22 T 98.5 O2 100% on RA Physical Exam ❧ ❧ Gen: Alert, appears stated age and cooperative, obese, uncomfortable but in no distress. Could speak in full sentences but appeared tired. ❧ Head: Normocephalic, without obvious abnormality, atraumatic ❧ Eyes: Conjunctivae/corneas clear. PERRL, EOM intact. ❧ Throat: Lips, mucosa, and tongue normal; teeth and gums normal ❧ Neck: No adenopathy, no carotid bruit, unable to assess JVD secondary to body habitus, supple, symmetrical, trachea midline ❧ Lungs: Clear to auscultation bilaterally, no w/r/c ❧ Heart: Tachycardia, regular rhythm, S1,S2 normal, no S3/S4/m/r ❧ Abdomen: Obese, bowel sounds normal; soft, pain with deep palpation and manipulation of RL pannus, no erythema;; no masses, no organomegaly could be appreciated. Physical Exam ❧ ❧ Extremities: Atraumatic, no cyanosis or edema ❧ Pulses: 2+, symmetric radial and DP pulses bilaterally. ❧ Skin: Dry skin, no rashes ❧ GU: No lesions on labia, vaginal canal without erythema, scant white discharge, not foul smelling. Cervix closed, no discharge, purple in color. No tenderness with speculum. Could not perform bimanual 2/2 body habitus. Wet prep - no trich, <50% clue cells ❧ NEURO: Awake, alert, and oriented x4. Sensation intact to light touch. Reflexes are 2+ in biceps, patellar. Strength is 5/5 bilaterally in the upper and lower extremities. Cerebellar function intact to finger to nose. CN II-XII: intact Labs ❧ (7-25) (20-25) (13.5-17.5) 134 103 43 166 (10-11) (80-100) 5.8 12 2.25 (65-99) 10.6 114.6 (4.5-11) (25-28) (1.5) (5-6) 11 311 (24-32) (0.5-1.10) 43.2 18.9 (33-34) (11.5-14.5 ) AG 22 (35-46) Ca 9.5 Mg 2.6 Phos 3.0

N 70 L 10 M 3 E 1 B 1 bands 7 TP Alb TB AST ALT ALP 7.3 3.0 2.0 43 33 264 (3.4-5) (<1.3) (20-120) Labs cont’d ❧

UA: (<0.3) Sg 1.024 RBC 51-99 Beta-OH 1.87 pH 6.5 WBC 6-10 Trop 0.02 Prot 25 Sq >100 BNP 81 (0.3-2.4) Glu Neg Bact Neg Lactic acid 4.9 Ket 15 Casts 6-10 ABG on RA 7.25/27/95/95.8% Blood 250 (7.35-7.45)(35-45) Nitrite Neg Utox - negative Urobili 8.0 Admission ❧ ❧ Patient admitted to LSU Medicine ❧ CXR clear. ❧ ABG 7.25/27/95/11.8. ❧ BNP 80, recent ECHO normal. ❧ AGMA – anion gap 22. Likely from renal function and medications (recently stopped). Lactic acid 4.9. ❧ With leukocytosis and abdominal pain, cultures sent and empirically started on Vancomycin/Piperacillin- Tazobactam/Ciprofloxacin (renally dosed) Admission cont’d ❧ ❧ AKI on CKD3 - Creatinine increased at 2.2 (1.5 on discharge). FeNa 0.18%, no eosinophils. Started IVF. ❧ Elevated AP/Tbili, N/V - lipase 48. RUQ ultrasound was limited by patient’s body habitus, showed hepatomegaly (diameter of 19cm, CBD 2.9mm) Day 2 ❧ ❧ Blood Pressures low/nml with Tachycardia (90s-100s), oxygen saturations wnl ❧ DOE - unchanged ❧ Nausea and vomiting with minimal improvement. ❧ Pannus still TTP. ❧ Alk Phos and Tbili continued to increase. ❧ On broad spectrum abx, all cultures NGTD. ❧ Still on continuous NS IVF. Cr improved - 1.64 from 2.25 ❧ Renal consulted Day 3 ❧ ❧ CT abd with PO contrast ❧ Labs: - hepatic steatosis. No ❧ Bicarb 17 (12) bowel wall thickening or ❧ Lactic acid 6.8 (4.9) adjacent changes ❧ AG 19 (22) indicating inflammation ❧ CK 176 ❧ ABG on RA ❧ AST 48 (43) 7.29/30/125/14.4 ❧ ALT 30 (33) ❧ On IVF, improving ❧ Tbili 2.9 (2.0) creatinine 1.47 (1.64) ❧ AP 276 (264) ❧ Hepatotoxic meds discontinued - abx, statin, protonix. Day 4 ❧ ❧ Labs: ❧ Bicarb 12 (17) ❧ Lactic acid 8.2 (6.8) ❧ Anion Gap 23 (19) ❧ Creatinine 1.62 (1.47) ❧ AST 53 (48) ❧ ALT 30 (30) ❧ Tbili 3.4 (2.9) ❧ AP 290 (276) ❧ Given 3 amps of bicarb in D5 ½N ❧ L-carnitine, Vit B complex, Thiamine, Vitamin C supplementation started Day 5 ❧ ❧ Labs: ❧ Bicarb 15 (12) ❧ Lactic acid 3.5 (8.2) ❧ Anion Gap 22 (23) ❧ Creatinine 1.68 (1.62) ❧ AST 85 (53) ❧ ALT 35 (30) ❧ Tbili 3.6 (3.4) ❧ AP 290 (290) ❧ GI consulted - recommend HIDA Day 5 cont’d ❧ ❧ WBC 15.5, 3% bands. Afebrile. ❧ Piperacillin-Tazobactam restarted ❧ Blood Glucose readings ❧ Day prior: 147-186 on 15U Lantus and SSI ❧ Day 5: Elevated at 342 that afternoon ❧ Patient placed on BIPAP overnight Day 6 ❧ ❧ Labs: ❧ Bicarb 15 (15) ❧ Lactic acid 4.6 (3.5) ❧ Anion Gap 23 (22) ❧ Creatinine 1.98 (1.68) ❧ AST 130 (85) ❧ ALT 47 (35) ❧ Tbili 4.9 (3.6) ❧ AP 332 (290) ❧ WBC 14.9 (15.5), 0% bands (3%) ❧ ABG - 7.28/32/75/15 Day 6 cont’d ❧ ❧ ICU consulted ❧ Blood Glucose readings 261-342 ❧ UA shows persistent ketone ❧ Pulmonary consulted, no new recommendations Day 7 ❧ ❧ First episode of hypotension, 89/39 with a repeat read of 95/50 ❧ WBC 23.6, 12% bands. Afebrile. ❧ Linezolid started for possible panniculitis. ❧ Dermatology consulted for punch biopsy ❧ HIDA scan showed diffuse hepatocellular dysfunction. ❧ Autoimmune workup pending - AMA, ANA Day 7 cont’d ❧ ❧ Bicarb 15 (15) ❧ Lactic acid 4.2 (4.6) ❧ Anion Gap 25 (23) ❧ Creatinine 3.29 (1.98) ❧ AST 141 (130) ❧ ALT 58 (47) ❧ Tbili 6.9 (4.9) ❧ AP 365 (332) ❧ ABG - 7.23/29/86/12.1 ❧ Blood Glucoses: 280-301 ❧ UA with 15 ketones, beta OH 7.3 Trended labs ❧ Trended labs ❧ Trended labs ❧ Trended labs ❧ Trended labs ❧ Trended labs ❧ Trended labs ❧ Day 8 ❧ ❧ Bicarb 12 (15) ❧ Lactic acid 3.7 (4.2) ❧ Anion Gap 24 (25) ❧ Creatinine 3.81 (3.29) ❧ AST 151 (141) ❧ ALT 63 (58) ❧ Tbili 7.9 (6.9) ❧ AP 384 (365) ❧ WBC 22.5 (23.6), 10% (12%) bands Day 8 (cont’d) ❧ ❧ Blood Glucose 204-316 ❧ Continued to titrate insulin ❧ UA with 15 ketones, beta OH 7.76 ❧ Ammonia 218 ❧ ABG 7.16/30/80/10.7 ❧ BP 84/65, HR 117, Blood Glucose 316

❧ Trialysis catheter placed in Right Internal Jugular ❧ Transferred to ICU Day 8/9 -ICU ❧ ❧ Pt confused and tachypneic ❧ CRRT initiated – creatinine improved to 1.64 (3.81) ❧ Continuous BiPAP ❧ Insulin drip started - beta OH 4.96 (7.76) ❧ Lactulose started - ammonia improved to 107 (218) Day 8/9 cont’d ❧ ❧ Bicarb 16 (12) ❧ Lactic acid 4.0 (3.7) ❧ Anion Gap 17 (24) ❧ AST 131 (151) ❧ ALT 66 (63) ❧ Tbili 8 (7.9) ❧ AP 424 (384) ❧ WBC 23.8 (22.5), 13% (10%) bands. Afebrile. Day 9 ❧ ❧Patient went into asystole and was unresponsive ❧Code was called and several rounds of ACLS were performed with multiple amps of NaHCO3 given due to her profound metabolic acidosis ❧Patient never regained ROSC ❧Patient died ❧Autopsy was not performed per the family’s request Final Diagnosis ❧ ❧Metabolic Acidosis ❧Lactic acidosis => ? mitochondrial dysfunction due to antiretroviral therapy ❧ ❧ Thank You LACTIC ACIDOSIS ❧ ❧Most common cause of metabolic acidosis in hospitalized patients. ❧Associated with: ❧Elevated anion gap ❧Plasma lactate > 4 meq/L ❧Leads to: ❧Impaired tissue oxygenation ❧Cause increased anaerobic metabolism ❧Source of rise in lactate production Pathophysiology ❧ ❧Factors that accelerate pyruvate production and simultaneously impair mitochondrial oxidation, thereby increasing pyruvate and lactate generation include: ❧Inadequate oxygen delivery or utilization ❧Rapid oxidation of certain substrates ❧Such as ethanol. Pathophysiology Cont. ❧ ❧ When lactic acid accumulates in body fluids and its concentration increases ❧ Hydrogen ions are almost completely buffered by extracellular bicarbonate. ❧ When lactate is utilized a hydrogen ion is also consumed.

❧ Whether by oxidation to CO2 and water or conversion to glucose or alanine ❧ Thus utilization of the lactate will restore the bicarbonate concentration. ❧ Excess lactate can accumulate as a result of increased production and/or diminished utilization ❧ Three mechanisms can cause this accumulation: ❧ Increased pyruvate production ❧ Reduced entry of pyruvate into mitochondria, where it would be converted to either carbon dioxide and water or to glucose precursors ❧ A shift of the cellular redox state such that NADH accumulates, which drives the pyruvate/lactate ratio toward lactate Causes ❧ ❧The causes of lactic acidosis can be divided into: ❧Those associated with obviously impaired tissue oxygenation (type A) ❧Those in which systemic impairment in oxygenation does not exist or is not readily apparent (type B)

TYPE A Lactic acidosis ❧ ❧Type A lactic acidosis ❧Most cases d/t marked tissue hypoperfusion in: ❧Shock ❧due to hypovolemia, cardiac failure, or sepsis ❧Or during a cardiopulmonary arrest. ❧Concurrent respiratory acidosis can contribute to the acidemia ❧Prognosis generally poor unless tissue perfusion rapidly restored. ❧Initial serum lactate level is a strong predictor of survival in patients with septic shock Type B lactic acidosis ❧ ❧Evidence for systemic hypoperfusion is not apparent in type B lactic acidosis. ❧Mechanisms that may be involved include ❧Toxin-induced impairment of cellular metabolism ❧Regional areas of ischemia Type B lactic acidosis ❧ ❧Metformin induced ❧Risk very low ❧More common with phenformin ❧Symptoms nonspecific and may include: ❧Anorexia, nausea, vomiting, abdominal pain, lethargy, hyperventilation, and hypotension. ❧Serum lactate usually < 2 mmol/L ❧More serious lactic acid accumulation occurs w/: ❧Superimposed shock or ❧Presence of predisposing conditions to metformin toxicity below Type B lactic acidosis Metformin induced ❧ ❧Has high fatality rate. ❧Most cases have occurred in patients with shock or tissue hypoxia or in the presence of several other predisposing conditions ❧ Impaired renal function ❧ Cr of 1.4 mg/dL in women and 1.5 mg/dL in men ❧ Concurrent liver disease or alcohol abuse ❧ Heart failure ❧ Use has been common and well tolerated ❧ Decreased tissue perfusion or hemodynamic instability due to infection or other causes ❧ Past history of lactic acidosis ❧ Of these factors, impaired renal function is of greatest concern ❧ Heart failure least worrisome. Type B lactic acidosis Metformin induced ❧ ❧Treatment ❧ Role of bicarbonate therapy in patients with lactic acidosis and shock or tissue hypoxia is not well established ❧ Concern about possible worsening of intracellular acidosis. ❧ Limit use to patients with: ❧ Severe metabolic acidosis (arterial pH below 7.10 to 7.15) ❧ Aim being to maintain the pH above 7.15, ❧ Until the acute toxicity resolves. ❧ In patients with concurrent renal failure, bicarbonate hemodialysis can both correct the acidosis and remove metformin ❧ HD should be used in patients who are: ❧ Critically ill ❧ Severe metabolic acidosis (pH <7.1) ❧ Fail to improve with supportive care or ❧ Renal insufficiency is present Type B lactic acidosis ❧ ❧Malignancy ❧ Pathogenesis is unclear ❧ Rarely occurs with rarely leukemia, lymphoma, and solid malignancies ❧ removal of the tumor (by chemotherapy, irradiation, or surgery) usually corrects the acidosis ❧ETOH ❧ Mild degree may develop in chronic severe alcoholism. ❧Lactate production usually normal ❧Lactate utilization may fall as a result of hepatic dysfunction. ❧Oxidation of ethanol can increase NADH levels and reduce the NAD+/NADH ratio. ❧This will shift pyruvate toward lactate. ❧ Lactate levels do not exceed 3 meq/L in these patients. ❧ Alcohol ingestion can potentiate the severity of other disorders that cause overproduction of lactate Type B lactic acidosis ❧ ❧Antiretroviral medication-induced mitochondrial dysfxn ❧Typically occur in absence of systemic hypoperfusion ❧Without intervention, leads to a fatal outcomes ❧Most often due to liver failure and cardiac arrhythmias. ❧Risk Factors: ❧Associated with exposure to dideoxynucleosides (NRTI’s) ❧Female gender ❧Advanced immunosuppression ❧Hepatic steatosis ❧ Possibly ethnicity. Type B lactic acidosis ❧ ❧Symptoms may be nonspecific and include: ❧Nausea, vomiting ❧Abdominal pain or liver failure ❧Aminotransferases are only mildly abnormal in most cases ❧Weight loss ❧Severe fatigue ❧Extertional dyspnea ❧Hyperventilation ❧Arrhythmias ❧Usually follows a minimum of six months of treatment ❧May occur precipitously Type B lactic acidosis ART-induced ❧

❧ Gold standard for the diagnosis of nucleoside- related mitochondrial toxic effects (Lactic Acidosis, etc) is a muscle or liver biopsy ❧Tx for Asxs Lactic acidosis ❧Substitution of the implicated nucleoside analogue w/ alternative drug in the same class that has less mitochondrial toxicity is recommended. ❧ lactate levels slowly normalized ❧Can consider: ❧ An all together alternate regimen or ❧ ART may be discontinued temporarily ❧Treated with medications, which may have a benefit on mitochondrial function (eg, riboflavin, carnitine, thiamine, coenzyme Q). Type B lactic acidosis ART-induced ❧ ❧Tx for Sxs for Lactic Acidosis ❧ ALL HIV meds should be stopped immediately and ❧ Close monitoring in a hospitalized setting ❧ For potential clinical progression, despite ART discontinuation ❧ Resolution of lactic acidosis after discontinuation can be extremely slow ❧ Reported experience is from 4 to 28 weeks ❧ Lactate level itself may be a risk factor for mortality ❧ No controlled trials to prove benefit but meds that support mitochondrial function should be given ❧ Anecdotal success has been described for combinations of: ❧riboflavin (50 mg daily) ❧L-carnitine (1000 mg twice daily), ❧thiamine (100 mg daily). ❧Easily available (also intravenously) and relatively harmless. ❧Survival also described with uridine (1000 mg three times daily) ❧Not easily available and cannot be given intravenously ART Induced Lactic Acid

❧ Bicarb Therapy ❧ ❧ The following general approach applies to the use of bicarbonate therapy: ❧ Who should be treated ❧ Lactic acidosis and severe acidemia (pH less than 7.1, but generally not those with higher values) ❧ may treat/prevent the following adverse clinical effects of acidemia, each of which can produce hemodynamic instability: ❧ Reduced left ventricular contractility ❧ Arrhythmias ❧ Arterial vasodilation and venoconstriction ❧ Impaired responsiveness to catecholamine vasopressors ❧ Goals of therapy ❧ Primary aim of therapy is reversal of the underlying disease (eg, shock). ❧ When using bicarbonate therapy in patients with lactic acidosis ❧ the aim is to maintain the arterial pH above 7.1 until the primary process causing the metabolic acidosis can be reversed. Bicarb Therapy ❧ ❧ Potential harms ❧ Rapid infusions of sodium bicarbonate may: ❧ Increase the PCO2 ❧ Bicarbonate must undergo several metabolic steps ❧ Generates CO2 that must be removed by circulation and respiration ❧ Adequate perfusion and ventilation is a prerequisite ❧ Even with adequate ventilation, PCO2 likely to rise at the local tissue ❧may worsen intracellular acidosis even as arterial blood pH inc ❧ In CSF ❧ At baseline a rise in arterial pH diminishes the drive for hyperventilation ❧Causing systemic PCO2 to increase. ❧Any systemic and/or local inc in PCO2 quickly reflected within CSF. ❧ Increased bicarbonate concentration is slowly transmitted to the CSF. ❧"paradoxical" CSF acidemia results from infused bicarb ❧ may be associated with neurologic deterioration Bicarb Therapy ❧ ❧ Potential harms ❧ Accelerate the production of lactate ❧ by reactivating glycolysis (which can produce LA) with inc pH ❧ Lower the ionized calcium ❧ Secondary to inc pH ❧ Can effect cardiac membranes ❧ Expand the extracellular space, and ❧ Raise the serum sodium concentration. ❧ Approach ❧ In adequately ventilated patients with lactic acidosis and severe academia: ❧ Give 1 to 2 meq/kg sodium bicarbonate as an intravenous bolus. ❧ repeat this dose after 30 to 60 minutes if the pH is still below 7.1.