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69
For ICU patients who are able to receive enteral medications and in whom stress
ulcer prophylaxis is indicated, an oral proton pump inhibitor (PPI) rather than an
intravenous H
2
blocker may be given. In contrast, for those who cannot receive
enteral medications, an intravenous H
2
blocker rather than an intravenous proton
pump inhibitor should be administered (Spirt and Stanley 2006 ). Antacids and
sucralfate are inferior to H
2
blockers and PPIs and are therefore not recommended
for the prevention of stress ulcers.
Stress ulcer prophylaxis is not recommended for medical or surgical patients
who are not in an ICU (Grube and May 2007 ) (Table 2.12 ).
2.11.3 Critical Drug Shortages
Drug shortages are nothing new but have become a growing and critical problem in
America. The list of drugs in short supply across all medical specialties is astound-
ing and includes antibiotics, anesthetic agents, antihypertensive medications, che-
motherapy agents, and common electrolyte solutions and vitamins.
In 2011, there were a record-high 267 new prescription drug shortages. This is 56
more than in 2010, when there were 211, and more than four times greater than the
number of medication shortages in 2004, when just 58 drug shortages were reported.
Table 2.12 Agents for stress ulcer prophylaxis
Agent Dosing
Adverse effects/comments
H
2
blockers Ranitidine 150 mg PO/NG Q12h or Mental status changes,
thrombocytopenia
50 mg IV q8h Dose adjust for renal
dysfunction
Famotidine 20 mg PO/NG/IV q12h Potential increased risk
of nosocomial pneumonia
Cimetidine* 300 mg PO/NG/IV q6h or *Only FDA label approved
agent for SUP
37.5–50 mg/h via
continuous infusion
Many drug-drug interactions
Proton pump
inhibitors (PPI)
Omeprazole 20 mg PO/NG daily Headache, diarrhea,
constipation, abdominal pain,
nausea
Esomeprazole 40 mg PO/NG/IV daily No adjustment needed for
renal or liver dysfunction
Lansoprazole 30 mg PO/NG daily Potential increased risk of
nosocomial pneumonia
Pantoprazole 40 mg PO/NG/IV daily Potential increased risk of
Clostridium diffi cile infection
Dexlansoprazole 30 mg PO daily Many drug interactions
Rabeprazole 20 mg PO daily
IV administration ONLY for
patients who cannot tolerate
PO/NG administration
*Cimetidine is the only agent with the FDA-labeled indication for stress ulcer prophylaxis
2 Cardiovascular Pharmacology
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The shortages have also delayed clinical trials that compare new, experimental
drugs to older ones and have led to extraordinary price extortion, causing many
hospitals to have to pay extremely large markups for limited drugs.
According to the FDA, the primary cause of the shortages is production shut-
downs due to manufacturing disruptions related to problems such as ingredient
microbial contamination and impurities or foreign particulates present in medicines
that prevent product quality from meeting FDA standards and regulations.
Shortages are also caused by companies that end production of drugs that have
small profi t margins, consolidation in the generic drug industry, as well as a short-
age of the raw materials used to make drugs.
Unfortunately, not many of the current shortages will be resolved soon due to
several key manufacturers that have had to shut down production because of con-
tamination or other quality problems. Some medicines may only have one other
manufacturer, which lacks the capability to fi ll the gap immediately or entirely.
The American Society of Health-System Pharmacists (ASHP) created the Drug
Product Shortages Management Resource Center ( www.ashp.org/shortage ) for
information related to drug shortages. This site, managed by the University of
Utah’s Drug Information Service (DIS), maintains the most comprehensive list of
scarce or unavailable drugs.
References
American Psychiatric Association: practice guideline for the treatment of patients with delirium
(1999) Am J Psychiatry 156(5 suppl):1–20
American Society of Health-System Pharmacists (1999) ASHP therapeutic guidelines on antimi-
crobial prophylaxis in surgery. Am J Health Syst Pharm 56(18):1839–1888
ASHP therapeutic guidelines on stress ulcer prophylaxis. ASHP Commission on Therapeutics and
approved by the ASHP Board of Directors on November 14, 1998 (1999) Am J Health Syst
Pharm 56(4):347
Bratzler DW, Houck PM (2004) Antimicrobial prophylaxis for surgery: an advisory statement
from the National Surgical Infection Prevention Project. Clin Infect Dis 38:1706–1715
Bruno JJ, Warren ML (2010) Intensive care delirium. Crit Care Nurs Clin North Am 22:
161–178
Cooper BE (2008) Review and update on inotropes and vasopressors. AACN Adv Crit Care
19(1):5–15
Dipiro JT, Talbert RL, Yee GC et al (2002) Pharmacotherapy: a pathophysiologic approach, 5th
edn. McGraw-Hill Co. Inc., New York
Edwards FH et al (2006) The Society of Thoracic Surgeons practice guideline series: antibiotic
prophylaxis in cardiac surgery, part I: duration. Ann Thorac Surg 81:397–404
Engelman R et al (2007) The Society of Thoracic Surgeons practice guideline series: antibiotic
prophylaxis in cardiac surgery, Part II: Antibiotic choice. Ann Thorac Surg 83:1569–1576
Falciglia M et al (2009) Hyperglycemia-related mortality in critically ill patients varies with
admission diagnosis. Crit Care Med 37(12):3001
Ganjehei L, Massumi A, Nazeri A, Razavi M (2011) Pharmacologic management of arrhythmias.
Tex Heart Inst J 38(4):344–349
Griesdale DE et al (2009) Intensive insulin therapy and mortality among critically ill patients: a
meta-analysis including NICE-Sugar study data. CMAJ 180:821
R. Fellin
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Grube RR, May DB (2007) Stress ulcer prophylaxis in hospitalized patients not in intensive care
units. Am J Health Syst Pharm 64:1396–1400
Havel C, Arrich J, Losert H, Gamper G, Müllner M, Herkner H (2011). Vasopressors for
hypotensive shock. Cochrane Database Syst Rev (5):Art. No. CD003709. doi:
10.1002/14651858.
CD003709.pub3
http://www.ashp.org/DocLibrary/Policy/PatientSafety/Optimizing-Med-Reconciliation.aspx
http://www.fda.gov/Drugs/DrugSafety/DrugShortages/ucm050792.htm
http://www.forbes.com/sites/dougschoen/2012/02/13/the-drug-shortage-crisis-in-america/
http://www.jointcommission.org/sentinel_event_alert_issue_35_using_medication_reconcilia-
tion_to_prevent_errors/
icudelirium.org. Available at:
http://icudelirium.org/index.html
Jacobi J et al (2002) Clinical practice guidelines for the sustained use of sedatives and analgesics
in the critically ill adult. Task Force of the American College of Critical Care Medicine
(ACCM) of the Society of Critical Care Medicine (SCCM), American Society of Health-
System Pharmacists (ASHP), American College of Chest Physicians. Crit Care Med
30(1):119
Kee VR (2003) Hemodynamic pharmacology of intravenous vasopressors. Crit Care Nurse
23:79–82
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Williams & Wilkins, Philadelphia
Kowey P (1998) Pharmacologic effects of antiarrhythmic drugs. Arch Intern Med 158(4):
325–332
Micromedex
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adult critically ill patient. Task Force of the American College of Critical Care Medicine
(ACCM) of the Society of Critical Care Medicine (SCCM), American Society of Health-
System Pharmacists (ASHP), American College of Chest Physicians. Crit Care Med
30:142–156
Ostermann ME, Keenan SP, Seiferling RA, Sibbald WJ (2000) Sedation in the intensive care unit:
a systematic review. JAMA 283(11):1451–1459
Overgaard CB, Davík V (2008) Contemporary reviews in cardiovascular medicine: inotropes and
vasopressors. Circulation 118:1047–1056
Poor K, Stanke S (2005) Understanding adult hemodynamics: a primer for cardiovascular surgery
and hemodynamic monitoring. TCHP Education Consortium
Rhoney D, Peacock W (2009) Intravenous therapy for hypertensive emergencies, part 1. Am
J Health Syst Pharm 66:1343–1352
Sessler CN (2005) Sedation, analgesia and neuromuscular blockade for high-frequency oscillatory
ventilation. Crit Care Med 33(Suppl):S209–S216
Spirt MJ, Stanley S (2006) Update on stress ulcer prophylaxis in critically ill patients. Crit Care
Nurse 26(1):18
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The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and
Treatment of High Blood Pressure (JNC VII). (2003) JAMA 289(19):2560–2572
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2012
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132(2):125–145
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Tsuneyoshi I, Yamada H, Kakihana Y, Nakamura M, Nakano Y, Boyle WA (2001) Hemodynamic
and metabolic effects of low-dose vasopressin infusions in vasodilatory septic shock. Crit Care
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345:1359
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in sepsis: an evidenced-based review. Crit Care Med 32(suppl):S554–S561
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A. Dabbagh et al. (eds.), Postoperative Critical Care for Cardiac Surgical Patients,
DOI 10.1007/978-3-642-40418-4_3, © Springer-Verlag Berlin Heidelberg 2014
Abstract
Pharmacoeconomics represents about the 15 % of health budgets of many nations
(Chunningham 2001). This is particularly relevant for patients with multiple
chronic conditions taking on average more medications or critically ill patients
that could have a long-term hospital or intensive care units (ICU) stay (Johnson
2002). In this chapter an overview on pharmacoeconomics is presented correlat-
ing the choice of i.v. fl uid to costs. It is possible to reduce signifi cantly the costs,
optimizing clinical benefi ts.
Pharmacoeconomics represents about the 15 % of health budgets of many nations
(Chunningham 2001 ). This is particularly relevant for patients with multiple chronic
conditions taking on average more medications or critically ill patients that could
have a long-term hospital or intensive care units (ICU) stay (Johnson 2002 ).
The key concept in pharmacoeconomics is the opportunity cost, which refers to
the added costs and benefi ts of a new treatment, over and above the already existing
ones.
Costs can be classifi ed as follows:
Direct : costs spent by health-care funder for a specifi c service or goods including
drug acquisition costs.
F. E. Agrò , MD (*) • M. Vennari , MD • M. Benedetto , MD
Anesthesia, Department of Intensive Care and Pain Management ,
Campus Bio-Medico of Rome , Via A. Del Portillo , 200 00128 Rome , Italy
e-mail: f.agro@unicampus.it; m.vennari@unicampus.it; m.benedetto@unicampus.it
3
Principles of Pharmacoeconomics
Felice Eugenio Agrò , Marialuisa Vennari ,
and Maria Benedetto
Contents
References ................................................................................................................................ 76
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74
Indirect : costs that are not directly related with a specifi c object such as costs for
administrative staff, equipment rental, and cost of travel to hospital.
Intangible : costs that are unquantifi able because they cannot be related to a specifi c
service or good such as engineering costs. These cannot be measured in terms of
money, but only in terms of quality of life.
The expected benefi ts from an intervention might be measured in:
Natural units – which refer to tangible events such as years of life saved, strokes
prevented
Utility units – which refer to the quality of health status
The quality-adjusted life year (QALY) is the most common measure used in health
economics, which includes both quality and quantity of life. It corresponds to esti-
mated survival x estimated quality of life (relative to “perfect health”) (Agrò 2013 ).
The costs and benefi ts or outcome analyses are performed using the following
four common types of economic evaluation:
– Cost minimization analysis (CMA): it compares costs of different strategies
which are clinically equivalent. As expected, the cheapest therapy is generally
preferred.
– Cost-effectiveness analysis (CEA): it is a type of evaluation, through which
health benefi ts are considered in natural units (e.g., years of life saved), whereas
the costs are considered in terms of money. The key measure is the incremental
cost-effectiveness ratio (ICER) which corresponds to (cost of drug A − cost of
drug B)/(benefi t of drug A − benefi t of drug B).
The four possible results arising in CEA are the following:
1. If costs of a new drug are lower and health benefi ts are higher, this would be the
preferred treatment.
2. If the new drug is more expensive and less effective, this is not recommended.
3. Commonly, a new drug is more effective but more expensive than the standard
treatment. Based on ICER, it is necessary to determine if the extra benefi ts jus-
tify the additional costs, i.e., if the new drug is “cost-effective.” It could be eval-
uated by a threshold value previously established.
4. Finally, the new drug is more expensive but more effective than the standard
treatment. This case is similar to the third one; it should be assessed that the extra
benefi ts provided by the standard treatment justify the additional costs of retain-
ing it as the preferred drug.
• Cost–utility analysis (CUA): it considers a specifi c outcome, evaluating the costs
to reach the goal measured in money. However, in this analysis, the outcome is
measured in terms of survival and quality of life. Thus, the outcome may not be
directly related to health status and cost–utility analysis can compare strategies
in different areas of medicine.
• Cost–benefi t analysis (CEA): it refers to the economic benefi ts of a strategy, and
costs and benefi ts are expressed in money. Cost–benefi t analysis may not account
for intangible costs that cannot be measured in terms of money (i.e., relief of
anxiety). This approach is rarely used in health economics.
In the critical care of cardiac patients, an important role is exerted by fl uid man-
agement, besides vasoactive drugs. Cost is one of the main concerns in making
decision for fl uid therapy (Agrò 2013 ). Only few reports compared the total costs of
F.E. Agrò et al.
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75
care adopting different fl uid therapies (Vincent 2000 ). In addition, no data exists on
costs associated with late outcomes, including those incurred after ICU or hospital
discharge. In particular, the widespread use of balanced solutions has caused con-
cerns about their expensiveness. The clinical benefi ts related to their use, however,
are expected to overcome the increased costs. The cost-effectiveness of balanced
solutions should be rigorously addressed taking into account potential advantages in
outcomes such as morbidity, mortality, and length of ICU or hospital stay, when
compared to unbalanced ones (Burchardi and Schneider 2004 ).
In fact, a large amount of 0.9 % saline and colloids dissolved in isotonic saline
(unbalanced) is associated with the development of dilutional–hyperchloremic aci-
dosis. Although moderate, this transient side effect (24–48 h) may increase the
length of ICU stay (Guidet 2010 ). Several reports indicated that this condition may
have detrimental effect on patients’ clinical course. Patients receiving balanced
solutions showed improved gastric and renal perfusion, thus reducing the incidence
of renal impairment. In addition, these solutions better preserved the hemostasis
when compared to unbalanced ones (Grocott 2005 ). All these aspects may translate
into prolonged length of hospital stay. The cost–benefi t ratio of plasma-adapted and
balanced fl uid therapy can vary from country to country according to the cost of
fl uids on the market and the clinical condition of the patients.
As an example, assuming that in Europe:
– An ICU stay cost of € 1,000/death
– An unbalanced plasma-adapted colloid or crystalloid cost of € 7
– A balanced plasma-adapted colloid or crystalloid cost of € 10
– A mean of hospital stay length of 3 days and 3 L/day fl uid therapy in patients
with multiple chronic diseases
The results are expressed in the following Table 3.1 :
The use of unbalanced and no plasma-adapted solutions leads to one additional
day of hospital stay because of the onset of metabolic and acid–base disorders. The
overall cost assuming unbalanced solutions as fl uid therapy corresponds to
(3,063 + 1,000 + 21) = 4,084 €, with a saving of 4,084 − 3,090 = 994 € using balanced
and plasma-adapted ones.
The result of cost–benefi t analysis on fl uid therapy may be summarized into the
following formula that can be used by single institutions to evaluate cost saving
related with the use of balanced plasma-adapted solutions (Agrò 2013 ):
Costsavingper year / $ = * 0.15*CDS / $ * *EXC / $‹‹‹
[] [] []
ndL−
Table 3.1 Difference in recovery costs using balance or unbalaced solutions. From Agrò et al. ( 2013 )
Unbalanced and no
plasma-adapted solutions
Balanced and plasma-adapted
solutions
Cost of hospital stay/die 1,000 € 1,000 €
Cost of FT/die 21 € 30 €
CostHS for 3 days (1,000 × 3) = 3,000 € (1,000 × 3) = 3,000 €
CostFT for 3 days (21 × 3) = 63 € (30 × 3) = 90 €
Total Cost (3,000 + 63) = 3,063 € (3,000 + 90) = 3,090 €
3 Principles of Pharmacoeconomics
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76
Assuming that:
• EXC is the extra cost of 1 L of balanced plasma-adapted solutions.
• L is the overall amount of fl uid therapy per day expressed in liter.
• CSD is the cost of hospital stay per day.
• n is the number of patients/year.
• d is the average number of hospital stay length.
In addition, we can use the following table reposting the maximum ratio (μ)
between extra cost and hospital stay cost for each combination of hospital stay
length and average amount of fl uid therapy per day. Taking into account site- specifi c
average hospital stay length (day) and average amount of fl uid therapy per day
(liter), we can obtain site-specifi c μ.
Multiplying μ * site-specifi c hospital stay cost per day, we obtain the cutoff value
of extra cost in order to gain the cost saving (Agrò 2013 ) (Table 3.2 ).
In conclusion, allowing faster patient discharge (hospital stay can be decreased
of few hours or even days), we can reduce signifi cantly the costs with optimizing
benefi ts in terms of patient outcome.
References
Agrò FE (2013) Body fl uid management – from physiology to therapy. Springer, Rome
Agrò FE, Benedetto U, Candela C (2013) Pharmaco-economics. In: Agrò FE (ed) Body fl uid man-
agement – from physiology to therapy. Springer, Milan
Burchardi H, Schneider H (2004) Economic aspects of severe sepsis: a review of intensive care
unit costs, cost of illness and cost effectiveness of therapy. Pharmacoeconomics
22(12):793–813
Chunningham S (2001) An introduction to Economic Evaluation of Health Care JO 3:246
Grocott MPW (2005) Perioperative fl uid management and clinical outcomes in adults. Anesth
Analg 100:1093–1106
Guidet B (2010) A balanced view of balanced solutions. Crit Care 14:325
Johnson RW (2002) Chronic conditions: making the case for ongoing care. Foundation Partnership
for Solutions. Princeton, NJ
Vincent JL (2000) Fluid management: the pharmacoeconomic dimension. Crit Care 4(2):S33–S35
Table 3.2 Presentation of costs according to length of hospital stay and liters of solutions admin-
istered per day. From Agrò et al. (
2013 )
Length of stay (day)
Amount of fl uid (L/day)
1 L/day 2 L/day 3 L/day 4 L/day
1 Day 0.15 0.075 0.05 0.0375
2 Days 0.075 0.0375 0.025 0.01875
3 Days 0.05 0.025 0.016667 0.,0125
4 Days 0.0375 0.01875 0.0125 0.009375
5 Days 0.03 0.015 0.01 0.0075
6 Days 0.025 0.0125 0.008333 0.00625
7 Days 0.021428571 0.010714 0.007143 0.005357
F.E. Agrò et al.
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77
A. Dabbagh et al. (eds.), Postoperative Critical Care for Cardiac Surgical Patients,
DOI 10.1007/978-3-642-40418-4_4, © Springer-Verlag Berlin Heidelberg 2014
A. Dabbagh, MD
Department of Anesthesiology and Anesthesiology Research Center, Faculty of Medicine,
Shahid Beheshti University of Medical Sciences, Tehran, Iran
e-mail: alidabbagh@yahoo.com, alidabbagh@sbmu.ac.ir
4
Cardiovascular Monitoring
Ali Dabbagh
Contents
4.1 Noninvasive Blood Pressure Monitoring ...................................................................... 78
4.1.1 Automated Blood Pressure Measurement ......................................................... 79
4.2 Invasive Blood Pressure Monitoring ............................................................................. 80
4.2.1 Common Indications and Contraindications for IBP Measurement
and Arterial Line Cannulation
.......................................................................... 81
4.2.2 Technique and Sites of Measurement (Sites of Cannulation),
Their Preferences, and Their Potential Complications ..................................... 82
4.2.3 Complications ................................................................................................... 85
4.2.4 Technical Considerations in Arterial Line Cannulation .................................... 86
4.2.5 Arterial Line Transducers and the “Coupling System”..................................... 87
4.3 Central Venous Pressure Monitoring ............................................................................ 88
4.3.1 Indications for CVC Insertion and Usage ......................................................... 89
4.3.2 Central Venous Pressure Curves ....................................................................... 89
4.3.3 Technical Considerations for Insertion of CVC ................................................ 90
4.3.4 Ultrasound-Guided CVC Insertion ................................................................... 94
4.3.5 Complications of CVCs .................................................................................... 95
4.4 Pulmonary Artery Pressure Monitoring ........................................................................ 98
4.4.1 History ............................................................................................................... 98
4.4.2 Clinical Outcome of PAC Usage ....................................................................... 98
4.4.3 Indications for PAC Use .................................................................................... 99
4.4.4 Contraindications of PAC .................................................................................. 99
4.4.5
Technical Considerations for PAC Insertion ..................................................... 99
4.4.6 Complications of PAC ....................................................................................... 103
4.5 Cardiac Output Monitoring ........................................................................................... 104
4.5.1 Fick Principle .................................................................................................... 105
4.5.2 Indicator Dilution Techniques ........................................................................... 105
4.5.3 Partial Carbon Dioxide (CO
2
) Rebreathing ....................................................... 107
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78
Abstract
One of the fundamental functions in each intensive care unit is monitoring, while
respiratory monitoring, cardiovascular monitoring, and cerebral monitoring are
the main three monitoring functions of ICU. In the current world of increasing
health technology, though, the exact and sophisticated examinations of the clini-
cians could not be replaced by any of these technologic improvements. A con-
tinual hemodynamic assessment after cardiac operations is a cornerstone of
postoperative cardiac surgeries. The main cardiovascular monitoring methods
involve – but are not confined to – the following pages, though more detailed
explanations could be found in details in related texts. Noninvasive and invasive
blood pressure, central venous and pulmonary artery pressure, cardiac output
monitoring modalities, and the normal range for measured hemodynamic vari-
ables are among the main topics that the reader could be familiar with after read-
ing this chapter.
4.1 Noninvasive Blood Pressure Monitoring
In 1896, Scipione Riva-Rocci described for the first time the measurement of sys-
tolic blood pressure using a cuff over the upper arm; also, in 1905, Nicolai Sergeivich
Korotkoff, a Russian surgeon, described the method of measuring blood pressure by
auscultation now well known as the Korotkoff sounds, from I to V, although
Korotkoff himself could recognize four stages which were “first sound, then com-
pression murmurs, second tone, and disappearance of sounds” and he could not
recognize the muffling which is phase II; these phases are frequently used in the
everyday clinic practice. The phase I of Korotkoff sound is equal to the systolic
pressure, which is the first stage of sound. During phases II and III of Korotkoff
sounds, the quality of the sounds changes. In phase IV of Korotkoff sounds, the
sound muffles, and in phase V, the sound disappears; in some pathologies like aortic
regurgitation, Korotkoff sound would be never discontinued, and so the final phase
is phase IV which is considered as the diastolic pressure. It has been demonstrated
that the Korotkoff sounds could be enhanced through a simple maneuver, i.e., “by
elevating the arm overhead in a 30-s period, then inflating the sphygmomanometer
cuff, and finally returning the arm to the normal position for blood pressure
4.5.4 Esophageal Doppler .......................................................................................... 108
4.5.5
Pulse Contour Analysis ..................................................................................... 109
4.5.6
Bioimpedance and Bioreactance ....................................................................... 110
4.5.7
Ultrasonic Cardiac Output Monitor (USCOM; USCOM Ltd.,
Sydney, Australia)
............................................................................................. 111
4.6 Selection of Cardiac Output Monitoring Modality ....................................................... 112
4.7 Normal Values for Hemodynamic Parameters .............................................................. 113
4.8 Transesophageal Echocardiography (TEE)................................................................... 114
4.9 Electrocardiography (EEG) .......................................................................................... 114
4.10
Near-Infrared Spectroscopy and Cerebral Oximetry .................................................... 114
References
................................................................................................................................ 114
A. Dabbagh
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