Failure Modes and Effects Analysis

(1)

Department of Neurology, Wake Forest University School of Medicine, Winston-Salem, NC, USA

Abstract

This chapter extends the principles of failure modes and effects analysis (FMEA) introduced in Chap. 2 with medical case examples. This chapter explores inductive reasoning or “forwards thinking” in the context of neurological diagnosis and treatment. FMEA facilitates understanding of symptoms from disease along physiological lines and helps predict effects on diverse organ systems. This facilitates treatment planning and implementing mitigation strategies in cases where the underlying disease itself is not directly treatable. It provides a framework to understand symptoms from a systems failure perspective, thereby optimizing the treatment response and preventing over- and undertreatment. FMEA also helps understand and implement strategies to anticipate, monitor, and mitigate side effects of many treatment regimens.

Keywords

Failure modes and effects analysis (FMEA)FMEA for prednisoneFMEA for IVIG therapyTherapy planningSide effect mitigationInflammatory neuropathyDiabetic lumbosacral radiculoplexus neuropathy (DLRPN)Myasthenia gravisParkinson’s diseaseAutonomic dysfunction

Introduction

Chapter 2 introduced failure modes and effects analysis (FMEA) from a systems safety assessment (SSA) perspective. It presented an application of FMEA in performing SSA for treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) with pulse steroids. FMEA helped identify diverse failure modes, failure severity, high-risk patient populations, and mitigation strategies in planning this intervention. This chapter extends the discussion on FMEA with more case examples spanning a more diverse spectrum of diseases. FMEA helps guide choice of therapy when there is a broad armamentarium of therapeutic strategies with a wide range of costs and side effects to choose from. In conditions where there is no direct treatment for the underlying disease, FMEA helps direct palliative and mitigation strategies which help quality of life and care. References [1–3] present the theoretical principles behind the method. As discussed in Chap. 2, failure classification to determine the consequences of failure is an integral part of FMEA. Chapter 1 presented safety assessment and failure classification for a range of critical industries ranging from aerospace, railways, nuclear, automobile, and industrial automation [4–7]. For the purposes of this chapter, we adopt a similar failure classification methodology with minor changes to adapt them to clinical medicine and neurology [1–7]. The following framework shown in Table 4.1 is used in this chapter, adapted from Chaps. 1 and 2.

Table 4.1

Failure classification adapted for medical applications from US FAA’s AC 25.1309

Failure classification	Effect on patient	Comments
Catastrophic	High probability of loss of life despite all corrective medical interventions	1. Faults, errors triggering catastrophic consequences must be extremely rare 2. Extremely rare is defined to be probability of occurrence in the 10⁻⁴ to 10⁻⁶ (probability of occurrence in the thousands or millions) 3. From Chaps. 1 and 2, catastrophic events must not happen from single point failure or simple combination of failures in dependable systems 4. Systems resulting in catastrophic consequences (humans, procedures, medications) must confirm to the highest skill, operational guidelines, and quality levels, equivalent to DAL A in the computer and engineering literature
Hazardous	Moderate risk for loss of life; permanent damage to vital organ systems like liver, kidney, heart especially if not urgently corrected and mitigation strategies effectively deployed	1. Faults and errors triggering hazardous consequences must be extremely rare, similar to catastrophic category 2. Rest as above
Major	Low potential for loss of life; reversible but moderate to severe damage to vital organ systems like heart, liver, kidney. This also includes conditions with lasting impact such as development of hypertension, diabetes mellitus, coronary artery disease, etc.	1. Faults and errors triggering major consequences must be rare 10⁻² to 10⁻³ (probabilities in the 100s to 1,000s) 2. Rest as above
Minor	No potential for loss of life; reversible, mild, abnormalities in vital organ systems like heart, liver, kidney. This also includes conditions with lasting impact such as development of mild edema, impaired glucose tolerance, osteopenia, and mild osteoporosis	1. Faults and errors triggering minor consequences can be more frequent than major category: 10⁻¹ to 10⁻² (probability of occurrence in the 10s to 100s) 2. Corresponding DAL can be lower 3. Single point failure is permissible
No safety effect	No potential for loss of life, no effect on major organ systems. Effects limited to pain, discomfort lasting a few days to week. Symptoms easily mitigated with rest, fluids, analgesics, and antidotes	1. Faults and errors triggering such events may be frequent 2. Single point failure is permissible 3. Lowest possible DAL

Failure classification intimately links to allowable probabilities of occurrence in terms of triggering faults and errors and corresponding development assurance levels (DAL—see Chap. 1)

FMEA in Therapy Planning

This section explores using FMEA for treatment planning in situations with a wide range of side effects ranging from no safety effect to catastrophic. This is especially advantageous for the treatment of chronic conditions with medicines having side effects which are dependent on dosing and duration. Casting the treatment in an FMEA framework has the advantage of classifying them by significance and directing mitigation strategies accordingly. Consider the example of two commonly used therapies in neuromuscular medicine—prednisone and intravenous immunoglobulin (IVIG).

FMEA for Prednisone Therapy

Prednisone is one of the most frequently used medicines in immunosuppression for the treatment of a wide range of inflammatory and autoimmune conditions across a variety of specialties. Prednisone is cheap, available in oral formulation, with well-recognized and predictable side effects. These include effects on numerous organ systems: cardiovascular, endocrine/metabolic, musculoskeletal, ocular, gastrointestinal systems among others. Additionally, immune suppression from prednisone increases the susceptibility to many infections. Generally, operating practice has been to use prednisone for cases where the benefit exceeds the risk, the side effects themselves being considered to some extent inevitable. Adopting the FMEA methodology, it is possible to mitigate side effects of prednisone to a great extent and deploy it effectively against a barrage of diseases, even in diabetic patients. FMEA report on prednisone can be created from a review of the literature [8] and is shown in Table 4.2. While the following is adapted from the myasthenia gravis literature, the methodology has potentially widespread application [8].

Table 4.2

FMEA approach to prednisone therapy

Failure mode	Failure classification/failure frequency	Patient responsibility	Physician responsibility	Comments
Abnormal blood glucose	Major (wide fluctuations possible, ranging from mild elevation to life threatening coma ~1,000 mg/dL) Frequency: extremely common	1. Maintain blood glucose log 2. Reduce calorie intake. Follow suggested nutrition recommendations	1. Check basic metabolic profile, HBA1c, random glucose 2. Encourage purchase of glucometer 3. If patient does not have glucometer, provide prescriptions for checking blood glucose once a week to every 2 weeks	1. If already diabetic, closely monitor sugar profile 2. May require additional insulin in the form of sliding scale, long-acting insulin. Work closely with endocrinologist
High blood pressures	Minor (higher average pressures, rarely in hypertensive urgency range) Frequency: extremely common	1. Monitor blood pressures once a day if hypertensive, once a week if normotensive 2. Reduce salt intake	1. Adjust antihypertensive dosing if patient is already hypertensive	1. Consider adding a diuretic for improving blood pressure control 2. Apply defense in depth (see Chap. 9)
Bone loss	Minor to major Frequency: extremely common	1. Calcium and vitamin D intake 2. Bisphosphonates as indicated by age and sex, baseline bone health	1. Consider baseline DEXA scan in high-risk populations 2. Annual DEXA scan 3. Check vitamin D level	Educate patients about bone health, benefits of exercise
Weight gain	Major Frequency: extremely common	1. Monitor calories. Low calorie, low fat, high-protein diet 2. Follow nutrition recommendations (see Appendix of Chap. 9) 3. Maintain weight chart	1. Closely monitor weight during each visit 2. Monitor and encourage compliance with nutrition	Request formal nutrition consult if there is excessive weight gain between visits
Cataracts/glaucoma	Minor to major Frequency: common	1. Regular eye exams, especially if diabetic	1. Monitor closely
Aseptic necrosis of hip	Major Frequency: rare	Inform physician of any new hip pain	Obtain X ray hip if there is new development of hip pain	May require hip replacement
Vertebral compression fractures	Minor to major depending on severity Frequency: generally uncommon except in prior osteoporosis	Inform physician of any new persistent back pain	Obtain X-ray Thoracic and Lumbar spine for any new back pain, observed loss of height	High-risk populations include women with prior osteopenia/osteoporosis
Fluid retention/leg swelling	Minor Frequency: common	Monitor weight Reduce salt intake	Consider low-dose diuretic
Abdominal pain/heartburn, nausea	Minor to major Frequency: very common	1. Over the counter omeprazole for steroid ulcer prophylaxis 2. Inform physician if there is new or severe heartburn	Reduce dose Monitor and treat for gastritis, steroid ulcer	Watch for bleeding in stools and vomitus
Easy bruising, thin skin	Minor Frequency: very common	None	None
Insomnia, mild anxiety, feeling wired	Minor Frequency: common	1. Reduce caffeine intake 2. Maintain sleep hygiene	Low-dose clonazepam, lorazepam while on high-dose steroid therapy	Reassurance, provide adequate counseling
Psychosis, steroid mania	Major Frequency: uncommon to rare	1. Stop prednisone 2. Inform physician 3. Seek assistance in ER immediately	1. Screen risk factors: prior bipolar disorder	Seek immediate psychiatry consult to prevent harm
Infection	Major Frequency: common	1. Watch for shingles, genital herpes and oral thrush break out. Inform physician immediately 2. Get killed flu vaccine 3. Avoid live vaccines	1. Monitor closely 2. Evaluate skin rashes immediately 3. Institute acyclovir or Valacyclovir prophylaxis in patients with frequent shingles or genital herpes outbreaks 4. Nystatin swish and swallow as first line for oral fungal infections. Consider adding oral fluconazole early if needed	Consider Trimethoprim/Sulfamethoxazole (Bactrim) prophylaxis for pneumocystis pneumonia
Addison’s crisis	Major Frequency: uncommon to rare	Inform physician of tiredness, weakness, or recent steroid therapy even if prednisone has been discontinued	Monitor closely. Blood cortisol levels. Monitor hypothalamic pituitary adrenal axis. Consider stress dose steroids, fluids for persistent hypotension	Consider Addisonian crisis in all patients with steroid therapy and hypotension
Miscellaneous Rare CNS infections like fungal meningitis, progressive multifocal leukoencephalopathy (PML), pseudotumor cerebri	Major Frequency: uncommon to rare	Inform physician about headache, somnolence, and change in mental status	MRI Brain Low threshold for spinal tap after MRI Brain for CNS infection	Educate patient and family about mental status changes

Failure modes, potential preventative and mitigating strategies are identified and instituted to prevent cascading failure. The prednisone FMEA should be used in conjunction with immunosuppression checklist discussed in Chap. 7. Prepared with assistance from David Mayans, MD. Adapted from [8]

The FMEA analysis demonstrated in Table 4.2 shows that prednisone therapy is best implemented in partnership between the patient and the physician. Failure modes can be viewed from patient and physician perspectives and responsibility devolved for mitigation strategies and timely intervention. It helps identify populations at higher risks and vulnerabilities such as patients with frequent shingles outbreaks, diabetes mellitus, hypertension, osteopenia, and helps institute specific preventive strategies. The prednisone information sheet has been successfully used in many of the case examples presented here.

FMEA for Intravenous Immunoglobulin Therapy

IVIG is used for a variety of autoimmune conditions in neurology, common examples being myasthenia gravis, Guillain-Barré Syndrome, CIDP among many others. Similar to steroid therapy, IVIG has a plethora of side effects ranging from minor to potentially life threatening. During the course of treating CIDP with IVIG and steroids, one fatality was seen. Based on the available EMS reports, it is possible that patient developed a deep venous thrombosis (DVT) and pulmonary embolism given reported symptoms of shortness of breath and cardiac arrest with pulseless electrical activity. An FMEA approach helps classify failure modes associated with IVIG and direct prevention and mitigation strategies accordingly [9]. This is shown in Table 4.3.

Table 4.3

FMEA for IVIG therapy, adapted from [9]

Failure mode	Failure classification/frequency	Risk factors	Mitigation strategy
Infusion-related symptoms (chills, nausea, myalgia, headache)	Minor Frequency: frequent	None	1. Plenty of fluids 2. Premedicate with IV Benadryl, oral acetaminophen 3. IV Methylprednisolone 50 mg if severe or IV Hydrocortisone 50–100 mg 4. Subcutaneous epinephrine if shock
Anaphylaxis	Major Frequency: infrequent	1. Common variable immunodeficiency 2. IgA deficiency	1. Although not mandated, consider checking IgA levels 2. IgA poor formulations
Thromboembolism (myocardial infarction, stroke, central retinal vein occlusion, deep venous thrombosis, pulmonary embolism)	Hazardous/catastrophic Frequency: 3 %	1. Elderly 2. Preexisting vascular disease 3. Immobility	1. Identify high-risk patients following IVIG checklist (see Chap. 7) 2. Monitor closely including EKG monitoring. Follow IVIG checklist for possible thrombotic complication
Reversible vasospasm	Minor to major Frequency: infrequent	None	MRI/MRA/MRV Brain Hydration
Headache, aseptic meningitis	Minor Frequency: frequent, up to nearly 60 %	None	NSAIDs IV Fluids
Abnormal renal function	Major Frequency: infrequent	1. Preexisting renal disease 2. Diabetes mellitus 3. Sepsis 4. Concomitant nephrotoxic drugs 5. Age > 65 years 6. Hypovolemia	1. Fractionate doses. Slow infusion rates 2. Maintain hydration 3. Sucrose-free formulations
Decompensated congestive heart failure	Hazardous/catastrophic Frequency: infrequent	1. Preexisting CHF 2. Unstable angina	1. Identify high-risk patients 2. Monitor closely in high-risk patients
Rash (urticarial, eczema, erythema multiforme, purpura, maculopapular rash)	Minor to major Frequency: ~6 %	None	1. IV Benadryl 2. Steroids
Hematologic	Major Frequency: rare	None	1. Monitor for hemolysis 2. Monitor for transfusion reactions 3. Monitor blood counts

The FMEA summary should be used in conjunction with IVIG checklist discussed in Chap. 7

Case Example 1: Treatment of Inflammatory Neuropathy Using FMEA Principles

PM is a 61 y/o diabetic female seen one and a half years after developing sudden onset of severe bilateral upper extremity weakness, numbness, and pain. Onset was abrupt, noticed on waking in the morning with a popping sensation in the neck followed by severe neck pain. She went to local urgent care and underwent X-rays of the neck. While waiting in urgent care, she experienced severe weakness, electric shock-like paresthesias initially in the right arm followed a few hours later by the left. During the course of hours, she developed severe bilateral upper extremity weakness. She denied any lower extremity symptoms. Prior to this illness, despite being diabetic she denied any numbness or tingling in her feet or hands. She reports ongoing electric shock-like painful paresthesias in her thumb and index fingers bilaterally with severe bilateral wrist drop and right greater than left shoulder weakness. MRI Cervical spine showed moderate degenerative changes in the neck without significant stenosis to explain the hand weakness and numbness.

Past medical history includes diabetes mellitus, stable coronary artery disease, s/p coronary artery bypass grafting (CABG) a few years ago, hypertension and hypothyroidism. She had undergone bariatric surgery also several years ago with weight loss. Medications included famotidine, insulin, hydrochlorothiazide, levothyroxine, a multivitamin, and potassium chloride. At the time, she was a current every day smoker.

Focused neurological examination revealed normal neck flexion and extension strength, deltoid strength. The right triceps had less than antigravity strength being 2/5, the left triceps showed mild weakness with MRC 4+/5 strength. Further distally she had absent movement with MRC 0/5 in the wrist extensors bilaterally. The wrists and fingers were maintained in flexion with little functional usage possible for the hands. Additionally, there was ulnar deviation of the wrist. The flexor pollicis longus showed 3/5 strength on the right, left was 4+/5; the Abductor Pollicis Brevis (APB) had only trace strength bilaterally with First Dorsal Interosseous showing 2/5 strength. These were tested with the hand passively placed in neutral position by extension of the wrist and fingers. The lower extremities showed normal symmetric strength in both legs. Deep tendon reflexes were normal in the biceps, absent elsewhere. The sensory examination was normal in the lower extremities and patchily decreased diffusely in the bilateral upper extremities.

Nerve Conduction/EMG study data is shown in Table 4.4.

Table 4.4

NCS/EMG report for Case Example 1

Nerve, stimulation site and side	Latency (normal limit)	Distance	Amplitude (normal)	Velocity (normal)	F waves
Median motor (right)
Wrist	5.1 (<4.4 ms)	70 mm	2.2 (>4.0 mV)		36.2 ms (<31 ms)
Elbow	10.4		1.3	41 m/s (>49 m/s)
Ulnar motor (right)
Wrist	4.2 (<3.5)	70 mm	4.4 (>6 mV)		33.0 ms (<32 ms)
Below elbow	8.6		3.8	44 (>49 m/s)
Above elbow	11.0		3.1	44 m/s
Ulnar motor (left)
Wrist	3.6 (<3.5)	70 mm	3.1 (>6 mV)		35.2 ms (<32 ms)
Below elbow	7.8		2.9	44 (>49 m/s): forearm segment
Above elbow	10.3		2.7	42 m/s
Tibial motor (left)
Ankle	6.6 (<6.0 ms)	80 mm	1.5 (>3.0 mV)	32 m/s	70.3 ms (<58 ms)
Pop fossa	18.6		1.2
Median sensory (right)	4.2 (<3.5 ms)	150 mm	3 (>22 μV)
Ulnar sensory (right)	Absent	140 mm
Radial sensory (right)	Absent	100 mm
Sural sensory (left)	4.5 (<4.2 ms)	140 mm	5 μV (>6 μV)
EMG findings
Muscle (side)	Description of findings
Deltoid, C6, C7 paraspinals (right)	Normal
Triceps (right)	1+ fibrillations, positive sharp waves; few normal motor units interspersed with enlarged polyphasic motor units with reduced recruitment
Biceps (right)	Absent spontaneous activity. Mildly enlarged but otherwise normal motor units with reduced recruitment
Extensor digitorum communis (right)	Profuse, 3 to 4+ spontaneous activity. Absent motor units
First dorsal interosseous	Absent spontaneous activity. Mildly enlarged motor units, essentially normal recruitment
Tibialis anterior, medial gastrocnemius, vastus lateralis (right)	Normal

Standard distances and normative data are within brackets for each nerve. The upper extremity nerves show mild demyelinating features with the lower extremities being more normal than the upper. This study was interpreted as a severe sensorimotor polyneuropathy with demyelinating features. Conditions in the differential include forms of chronic inflammatory demyelinating polyneuropathy (CIDP), idiopathic brachial plexitis (Parsonage Turner Syndrome) and diabetic cervical radiculoplexus neuropathy

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