Circulatory / septic

shock in heart failure.

Ashoka Benedict Gomes. 06/11/17.

PHA5591
History of present illness:

● RI is a 71 year male with history of CKD stage III (GFR between 30-59ml/min-baseline Cr~2), Combined systolic and
diastolic heart failure with EF 20-25% (severe) with an ICD, HLD, PAH group 2 (Pulmonary arterial hypertension -left),
CAD, CVA (2010, on xarelto), AFib, HTN, ischemic cardiomyopathy.

● RI was brought to the hospital by EMS from the dialysis center due to an incoherent altered mental state at dialysis; he was noted
to be paced by ICD at 40 bpm on arrival 7 days back; with SBP 104 and O2 sats in the 90's (low). He was paced at 50 bpm on
arrival improving his SBP to 70-90, pt is paced less than 1% by the ICD.
● He was treated with Levophed for shock and a broad spectrum Antibiotic. He was started on bumex 2 mg/hr ggt and on
Chlorothiazide to reduce fluid but did not diurese. 7 days back bumex ggt was stopped and CVVH (Continuous Veno-Venous
Hemofiltration) was started. Pt started self-diuresing 2 days back and CVVH was stopped. Levophed was gradually taken off. Blood
Cultures were positive for MRSA and Corynebacterium (likely contaminant). Zosyn was stopped 5 days back and Vancomycin will
continue for 14 days (no blood growth was seen 4 days back). Rivaroxaban (for Afib) was held at admission. Tube feeds were
started 5 days back and D10W is stopped when he is at goal feeds.

● RI is a 71 yr African-American male with a chief complaint of altered mental state with low SPB (104), bradycardia, acute renal
failure with hyperkalemia and is deaf-mute (needs interpreter).
Past Medical History (PMH):
He has a PMH significant for CKD stage III (GFR between 30-59ml/min-baseline Cr~2), CAD, CVA (2010, on xarelto), AFib,
HTN, ischemic cardiomyopathy, Combined systolic and diastolic heart failure with EF 20-25% (severe) with an ICD,
HLD, PAH group 2 (Pulmonary arterial hypertension -left).

Current Medical Problem List:

1- RI continues to have reduced heart function.
2- RI presented with low SBP pressure and an altered mental state with fluid overload.
3- He was diagnosed on admission with high TSH and put on thyroid medication.
4- RI has a blood infection with unknown cause.

Family History/Social History:

Health Plan: Medicaid.
Occupation: unemployed.
Race: African american.
Alcohol: None
Hobbies: Watching TV.
Primary Provider: Health center.
Family History: noncontributory.
Smoking: None
Illicit drug use: None

Allergies: NKDA.
Adherence: Patient is independent for ADL.
Immunization: Uptodate.
Current Medications:
1- Famotidine 20 mg Intravenous daily.
2- 0.9% NaCl IV @ 150 ml/hr continuous.
3- Levothyroxine 25 mcg orally in the morning.
4- Midodrine 2.5 mg orally every 6 hours.
5- Adult nutritional additives Per NG tube twice daily.
6- D10W 40 mL/hr.
7- Osmolite 1.5 Cal. continuous tube feed 40 mL/hr.
8- Adult nutrition continuous flush with option of additives 10 mL/hr as needed.
9- Docusate 100 mg twice daily as needed.
10- Senna 1 tab at night as needed.
11- polyethylene glycol as needed.
12- vancomycin as needed.
13- dextrose as needed.

Review of Symptoms:
General: PE: Signs/symptoms: WD.
Vital signs: T-97.5 P-60
RR-16
BP-95/57 mmHg O2sat- 97%
WT- 103kg HT- 68.11 inches.
Continued on next slide….
Review of symptoms:
ENT/mouth/neck/eye: moist mucous membranes no lesions, neck soft and supple. PERRL, EOMI (eye).
Neuro: moves upper extremity, minimal bilateral LE; alert, oriented to person/place, not time or event.
Blood work: TSH=15.
Respiratory: clear to auscultation, no wheezing.
Cardiovascular: non-tachycardic irregular, no murmur, nonpalpable pedal pulses, bilateral pitting edema.
Abd : BS+, abdomen soft, non-tender, non-distended.
Renal: Scr=~2.5. BUN=~20 mg/dl (CKD stage 3).
Psych : Alert.

Identification of Drug Therapy Problems:

1- Indication for a drug but drug not prescribed properly. (Patient is on midodrine for his hypotension and could benefit from an
increased dose).
2- Indication for a drug but drug not prescribed properly. (Patient is hypotensive with fluid overload but is receiving >3.6L/day
IV fluids, ACC/AHA guidelines recommend no fluid or less than 2L/day (ref=7)).
3- Indication for a drug but no drug prescribed. (Patient is hypotensive with stage D HF with fluid overload and should be
receiving a loop diuretic per ACC/AHA guidelines / DOSE study (Ref=7,8).
4- Indication for a drug but drug not prescribed. (Patient could benefit from oxygen therapy while in the hospital).
5- Indication for a drug but drug not prescribed properly. (Patient is using a high carb nutrition which is not recommended in
CKD 3 per Kdigo guidelines).
6- Indication for a drug but not prescribed properly. (Patient is on vancomycin which is renally eliminated but has stage 3 CKD
and could benefit from daptomycin administration).
Drug Therapy Problem #1:

Indication for a drug but drug not prescribed properly. (Patient is on midodrine for hypotension and could benefit from an
increased dose).

Based on the ACC/AHA guidelines for this patient and looking at the benefits based on clinical research an increase in dose will
be more efficacious at increasing the patient's blood pressure.
Pathophysiology of Stage D heart failure:

● Heart failure results when the heart due to a functional defect is unable to pump blood to meet the needs of the tissues
this usually results in fluid buildup in the tissues. HF can occur due to weakening of the heart muscles or the values of
the heart or when the electrical conductivity becomes abnormal. Over time there is end organ damage as the tissues do
not receive oxygenated blood and waste is poorly removed.

● Signs of HF include weakness, fatigue, variable pulse, pulmonary edema, fluid buildup and weight gain, chest
pain/pressure, tachycardia, shortness of breath, loss of appetite.

● Per the ACC/AHA guidelines HF is classified by stages A to D and treatment is based on the patient's condition with the
use of diuretics, ACEI / ARBs and b-blockers as the basis of pharmacological treatments. ICD or pacemakers are used
in some HF patients with good outcomes, but generally stage D HF patients have a high mortality and hospital
readmission rate. Fluid and salt restriction are also to be considered in the treatment of HF patients.
Intervention to resolve drug therapy problem: for #1
● Possible to increase the dose of midodrine to 5 mg every 6 hours to increase BP.
Rationale for intervention: Based on the ACC/AHA guidelines for this patient and looking at the benefits based on clinical
research an increase in dose will be more efficacious at increasing the patient's blood pressure.

Pharmacology of Midodrine:
Midodrine is a alpha 1 agonist, indicated for orthostatic hypotension due to its ability to increase BP by causing peripheral
vasoconstriction of blood vessels.
It is metabolized to a pharmacologically active compound “de-glymidodrine” which exerts its alpha 1 agonist actions.

Pharmacokinetics/dynamics of Midodrine:
Midodrine is orally absorbed and metabolized to de-glymidodrine.
It's time to peak serum concentration is 30 minutes with onset of action in about 1 hour and duration of action is 2-3 hours. It
does not cross the BBB and has low protein binding.
It is actively renally secreted in the urine (80%). In renal impairment consider a lower dose and gradually increase.

Preparation/administration/stability/cost of Midodrine:
MIdodrine is only available as a tablet in dose of 2.5 mg, 5 mg, and 10 mg. Its cost is low.
Scientific/Expert opinion: #1
1- Zakir, R. M., Folefack, A., Saric, M. and Berkowitz, R. L. The Use of Midodrine
in Patients With Advanced Heart Failure. Congestive Heart Failure, 2009, 15:3 pp
108–111.
Objective: The authors evaluated the use of midodrine to treat hypotension in
advanced heart failure patients, so that standard treatments for heart failure could
be used in the patients.

Methods: 10 HF patients (systolic dysfunction LVEF<35) with symptomatic

hypotension (sbp<85) were given Midodrine 5 mg q6h to a max of 10 mg q6h and
transthoracic echocardiography was performed at baseline and after 6 months.

Results: Treatment with midodrine resulted in a significant change after 6

months in SBP from 79.2 to 99 mmHg, DBP from 49.1 to 58.8, BNP from 1402 to
706, LVEF increased from 24% to 32.2%, total hospital days decreased from 150
to 58. ACE/ARB use as a % of optimal dose increased from 20% to 57.5%, β-
Blocker use as % of optimal dose increased from 37.5% to 75%, and
Aldactone/eplerenone use as % of optimal dose increased from 43.7% to 95%.

Conclusion: Based on the results it was concluded that using midodrine in

patients with symptomatic stage D HF allowed for higher doses of neurohormonal
agents more inline with the HF recommendations resulting in better outcomes for
the patients.
Scientific/Expert opinion: #2
2- Micah R. Whitson et al (2016). Feasibility, Utility, and Safety of Midodrine During Recovery
Phase From Septic Shock. CHEST 2016; 149(6):1380-1383.

Objective: To evaluate if using midodrine can decrease vasopressor treatment and length of ICU
stay in septic shock.

Methods: This is a two-arm retrospective study of 275 patients admitted to the ICU with septic
shock. Patients were put in 2 groups, 140 pts received an IV vasopressor only and 135 pts received
midodrine in addition to an IV vasopressor. Baseline characteristics were similar.

Results: Vasopressor-only IV group had a mean treatment of 3.8 days v/s 2.9 for vasopressor +
midodrine IV group (<0.001) which was significantly different.
Vasopressor-only IV group had a mean length of ICU stay (ICU-LOS) of 9.4 days v/s 7.5 for
vasopressor + midodrine IV group (p=0.017). And hospital LOS of 24.2 v/s 21.9 days (p=0.3).
Change in creatinine was not significantly different between groups indicating no renal effects with
midodrine.

Conclusion: The authors concluded that addition of midodrine can reduce the ICU-LOS and
vasopressor requirements in patients with septic shock.
Monitoring Plan:
Parameter Frequency

Continue CBC monitoring. Every day while in the hospital. To check electrolyte levels.

Monitor fluid input and output Every day while in the hospital. To measure the level of diuresis and fluid
status.

Blood pressure, pulse, SpO2. Every day while in the hospital. To monitor the effectiveness of the treatment
changes.
Drug Therapy Problem#2:
Indication for a drug but drug not prescribed properly. (Patient is hypotensive with fluid overload but is receiving >3.6L/day IV
fluids, ACC/AHA guidelines recommend no fluid or less than 1.5 to 2L/day (ref=7))

Rationale for intervention: Based on ACC/AHA guidelines for this patient (stage D HF) the recommendation is to restrict IV
fluids (ref=7).

Intervention to resolve drug therapy problem: for #2

Decrease IV fluid intake to 60 ml/hr or about 1.5L/day.
Pharmacology of sodium chloride IV fluids:
Sodium chloride is a sterile electrolyte solution used to replace the body with fluid and sodium chloride.
It is available as 0.9% saline solution which contains 9 grams of sodium per liter or 0.45% or 3-5% saline.
0.9% normal saline contains 154 mEq/L of Na+ and Cl− with a similar osmolarity as NaCl in blood.

Pharmacokinetics/dynamics of sodium chloride IV fluids:

Sodium chloride is well absorbed. It distributes widely in the body and is excreted in urine, tears, sweat, saliva.

Preparation/administration/stability/cost of sodium chloride IV fluids:

Sodium chloride is available as an IV infusion in different strengths (0.9%, 0.45%, 3-5%) or lactated ringer's solution. Sodium
chloride solution is also available as a tablet, nasal spray, eye drop, irrigation, nebulization, ointment, swab.
Sodium chloride IV is inexpensive.
Scientific/Expert opinion: #1 4- Behnood Bikdeli, et al. Intravenous Fluids in Acute Decompensated Heart
Failure. JACC: Heart Failure Feb 2015, 3 (2) 127-133.

OBJECTIVE: The study looked at the use v/s non-use of intravenous fluids in early acute decompensated
heart failure (HF) patients treated with loop diuretics on outcomes.

METHODS: This study was a retrospective cohort study of (131,430) patients treated in the first 2 days of
admission with IV fluids and loop diuretics. The primary outcome was the percent of hospitalizations using IV
fluids in the 1st 2 days and secondary outcomes were LOS, in-hospital death, critical care admission,
intubation, and renal replacement therapy.

Results: 11% of hospitalizations received IV fluids median volume of 1000 ml and 120 mg IV furosemide in
the 1st 2 days and rest received median 140 mg of IV furosemide and no fluids.
For outcomes: Median LOS was 4 days (3-7 days) for IV fluid treated group and 4 days (2-6 days) for no IV
fluid group. Patients that received IV fluids were associated with
higher critical care admissions (5.7 v/s 3.8% p<0.0001), (Odds Ratio 1.57 (95% CI: 1.45 to 1.71),
late intubation (1.4 v/s 1.0% p=0.0012), (OR 1.46 (95% CI: 1.25 to 1.71),
mortality (inhospital) (3.3 v/s 1.8% p<0.0001), (OR 2.02 (95% CI: 1.82 to 2.24),
renal replacement therapy (0.6 v/s 0.3% p<0.0001), (OR 2.04 (95% CI: 1.62 to 2.55), compared to patients
that did not receive IV fluids.

CONCLUSION: The authors concluded that IV fluid administration in patients hospitalized with HF in the first 2
days is associated with adverse outcomes. Which is consistent with the ACC/AHA guidelines to restrict fluid in
stage D HF patients.
Scientific/Expert opinion: #2
5- J. Arcand, J. Ivanov, A. Sasson, et al. A high-sodium diet is associated with acute decompensated heart failure in
ambulatory heart failure patients: a prospective follow-up study. Am J Clin Nutr, 93 (2011), pp. 332–337.

Objective: To analyze the risk of high sodium intake causing acute decompensated HF (ADHF). Secondary outcomes were
all-cause hospitalization and death.

Methods: Data from 123 stable HF patients using a standard HF medication treatment. Their dietary intake was measured by
2 (3 day) food records. Patients data were checked for outcomes of ADHF., hospitalization or death.

Results: Patients had a mean age of 60yrs, LVEF<25% and were grouped into tertiles depending on sodium intake as low=
mean 1.4 g Na/day, middle= 2.4 g Na/day, and high= 3.8 g Na/day. Baseline characteristics of these groups were similar.
ADHF events for low, middle and high sodium groups were 5%, 5% and 17% at 1 year and 12%, 15% and 46% at 3 years.
Multivariate Cox regression analysis of the high sodium intake group to the other 2 groups with all covariates resulted in a
hazard ratio(HR)=2.55 (95% 1.61 to 4.04 p< 0.001) for the primary endpoint of ADHF (and without covariates the HR was 1.66
(1.23-2.24) for the high sodium intake group), other events were non-significant.

Conclusion: The authors concluded that HF patients who had a high-sodium diet were 2.5 times more likely to have ADHF
compared to patients with lower dietary sodium.
Alternative Drug Therapy:
1- Possible to dialysis the patient to reduce fluid.
2- 0.45% sodium chloride solution could be used.
References:

1- JNC 8 guidelines.
2- JNC 8 guideline algorithm.
3-KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease.

4- 2016 ACC/AHA/HFSA Focused Update on New Pharmacological Therapy for Heart Failure: An Update of the 2013 ACCF/AHA Guideline for the
Management of Heart Failure.

5-Zakir, R. M., Folefack, A., Saric, M. and Berkowitz, R. L. The Use of Midodrine in Patients With Advanced Heart Failure. Congestive Heart Failure, 2009,
15:3 pp 108–111.

6- Oral vasopressor to accelerate liberation from the ICU. March 28, 2016 by Josh Farkas.

7-Clyde W. Yancy et al. 2013 ACCF/AHA Guideline for the Management of Heart Failure. A Report of the American College of Cardiology
Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;128:e240-e327.

8- G. Michael Felker et al (2011). Diuretic Strategies in Patients with Acute Decompensated Heart Failure (DOSE study). N Engl J Med March 3 2011;
364:797-805.