Transcript PAIN - KSUMSC

Lecture Title: Acute Pain Management
Lecturer name: Osama Ibraheim
MD,SOB.
Lecture date:
Lecture Objectives..
Fundamental Considerations
• Millions of patients worldwide
undergo surgery.
Although
developing
more
effective
techniques
for
postoperative analgesia, many
patients experience pain.
PAIN
An unpleasant
sensory and
emotional experience
associated with actual
or potential tissue
damage.
IASP, Subcommittee on Taxonomy, 1979
ETIOLGY OF PAIN
1.
2.
3.
4.
HEAT
COLD
CHEMICAL
MECHANICAL
TORSION STRETCH CUT PINCH
COMPRESS CRUSH
PRICK
TYPOLOGY OF PAIN
1. Acute
2. Chronic benign
3. Chronic cancer
Chronic Pain vs Acute Pain
Acute:
A Symptom of Injury or Disease
Chronic Benign: Pain itself is the disease
Chronic Cancer: Actual Tissue destruction
Adverse Effects of Pain
1.
2.
3.
4.
Cardiovascular
Pulmonary
Gastrointestinal
Renal
1.
2.
3.
4.
Extremities
Endocrine
CNS
Immunologic
Adverse Effects of Pain
Cardiovascular: Tachycardia, hypertension, increased
SVR, increased cardiac work, increased
myocardial O2 demand.
Pulmonary: Hypoxia, hypercarbia, atelectasis,
decreased cough, decreased vital capacity and
function residual capacity, V/Q mismatch.
Gastrointestinal: Nausea, vomiting, ileus, intolerance
for oral intake.
Renal: Oliguria, urinary retention.
Adverse Effects of Pain
Extremities: Skeletal muscle spasm, limited
mobility, thromboembolism.
Endocrine: Excessive adrenergic activity, vagal
inhibition, catabolic metabolism,
increased O2 consumption.
CNS:
Sedation, fatigue, anxiety, and fear cause
central sympathetic stimulation.
Immunologic: Inhibited cellular immunity,
increased risk of infection, ?? impaired
wound healing ??
FREE NERVE ENDINGS ARE
PRESENT IN ESSENTIALLY
ALL BODY TISSUES IN
VARYING AMOUNTS
IN RESPONSE TO A PAINFUL
STIMULUS, SUBSTANCES ARE
EXCRETED.
ALGOGENIC
(substances released by pain)
SEROTONIN
POTASSIUM
HISTAMINE
ACETLYCHOLINE
BRADYKININS
LEUKOTRIENES
PROSTAGLANDINS SUBSTANCE P29
NOREPINEPHRINE
THE RECEPTORS IN THE FREE NERVE
ENDINGS RESPOND TO THE
SUBSTANCES BY BECOMING CHARGED
ELECTROCHEMICALY
RECEPTORS THEN PROPAGATE AN
ELECTROCHEMICAL STIMULUS TO
DIFFERING NERVE FIBERS
NOCICEPTION
This electrochemical event that occurs
between the site of tissue damage or injury
sets off a series of neural transmissions that
eventually results in the perception of
pain……Collectively this known as
nociception
NERVE FIBER
PAIN CLASSIFICATION
A FIBER……..SHARP-STABBING-LOCAL
“ FIRST PAIN”
B FIBER....PHYSIOLOGIAL REACTION
C FIBER....DULL-ACHE-BURN-THROB
NONLOCALIZED-RADIATE
“SECOND PAIN”
NERVE FIBER CLASSIFCATION
TYPE
A a
A alpha
A beta
A delta
A gamma
myelinated
myelinated
myelinated
myelinated
myelinated
FUNCTION
motor
touch-pressure
touch-pressure
pain-temperature
proprioception
A Delta
1.
2.
3.
4.
5.
1 - 4 micrometers diameter
Myelinated, Rapid conduction
Sharp, localized
Heat, cold
“First pain”
B myelinated
preganglionic autonomic
C non-myelinated
pain-temperature
C Fibers
1. Small
2. Slow Conduction
3. Unmyelinated
4. Postganglionic autonomic
C Fibers
1.
2.
3.
4.
Dull pain, burning, Aching throbbing
Nonlocalized - radiating - diffused
Temperature,Touch,Mechanical
“Second pain”
Gate Theory
Balance between A delta and C fibers to
dorsal horn determines the intensity of
the stimulus that is passed to higher
brain center
Area of High Nociceptor
Concentration
1.
2.
3.
4.
5.
6.
7.
Mucosal membranes
Periosteum
Deep fascia
Ligaments
Joint capsules
Cornea
Subcutaneous tissue
Areas of Moderate Nociceptor
Concentration
1. Skeletal muscle
2. Cardiac muscle
3. Smooth muscle
Areas of Minimal Nociceptor
Concentration
1. Bone
2. Cartilage
3. Marrow
Physiologic Processes of
Nociception
1.
2.
3.
4.
5.
Detection
Transduction
Transmission
Modulation
Perception
Detection
1. “First pain”
2. “Second pain”
TRANSDUCTION
NOXIOUS STIMULI TRANSLATED INTO
ELECTRICAL FIRING AT THE SENSORY NERVE
ENDINGS
TRANSMISSION
1. PROPAGATION OF IMPULSE TRAVELS VIA
NEURAL PATHWAYS.
2. SENSORY AFFERENT NEURONS PROJECT
INTO THE SPINAL CORD
3. ASCENDING NEURONS RELAY TO BRAINSTEM
AND THALAMUS
4. THALAMUS RELAYS TO CEREBRAL CORTEX
MODULATION
INTRINIC PAIN MODIFICATION
1.DIFFERENT IN INDIVIDUALS
2.DEPENDS ON.....
PAST EXPERIENCES
CULTURE
PSYCHIC
MODULATION-CONT
1.
2.
3.
4.
5.
6.
7.
STIMULUS PRODUCED ANALGESIA
NEUROENDOCRINE ANALGESIA
CNS/PNS ANALGESIA
OPIOID ANALGESIA
SITUATION
PATHOLOGY
PHYSIOLOGY
Modulation – Excitatory Substances
1. Peripheral
Prostaglandins, bradykinins, histamine, K,
substance P, serotonin (5HT2)
2. Spinal
Glutamate, aspartate, amino acids, substance
P, norepinephrine (alpha 1)
Modulation - Inhibitory
Supraspinal
– Endorphins, enkephalins, dynorphins,
norepinephrine (alpha 2), GABA,
somatostatin (5HT1), neurotensin
First Neuron Pain
Peripheral afferent fibers to dorsal horn
Second Neuron Pain
Dorsal horn to thalamic
Third Neuron Pain
Thalamus to cortex
Pain Pathways:
• Tissue damage>>>Algesic substanses
release>>>Noxious stimuli>>>A delta and C
fibers>>>to the Neuraxis>>>Many to Ant. and
Anterolat.Horns>>>Segmenal reflex responses ,
and others via the Spinothalamic and
Spinoreticular tracts>>>Suprasegmental and
cortical responses.
Classification & Function of Peripheral
Nerve Fibers
A. Myelinated A- Fibers:
• a: Motor , Proprioception (afferent)
• b: Motor, Touch (afferent)
• g: Muscle spindles (efferent)
• d: Pain, Temperature (afferent)
B. Myelinated B-Fibers:
• Pre-ganglionic Sympathetic Fibers
C. Non-Myelinated C- Fibers: Pain, Temperature.
Nociceptive pathways: peripheral
Dorsal horn of
spinal cord
sensory nerves
Spinothalamic
tract
Nociceptive
Dorsal Root
Ganglion
Peripheral
nerve
Sympathetic ganglion
Viscera
Blood vessels
Skeletal
muscle
Tendon
bundle
Muscle and skin Nociceptive
terminals
receptors
C and Ad
fibres
sensory fibres are
C-fibres and Ad
fibres
C-fibres
umyelinated
Ad myelinated
Slow conduction
velocity
Signal variety of
noxious stimuli polymodal
Ascending Pain Pathways
Cortex
Thalamus
Mesencephalon
Pons
Medulla
oblongata
Spinal
cord
Topographic
representation
maintained
Sites for pain
modulation are
spinal cord and
thalamus
• Segmental reflex
responses:
Increased skeletal muscle
tone , Increased oxygen
consumption , Lactic acid
production
• Suprasegmental
• reflex responses:
Increased Sympathetic
tone , Hypothalamic
stimulation.
Chemical Mediators
Membrane ion channels of Nociceptive neurons
Directly coupling to membrane receptors
Hydrogen
• ATP
• Serotonin
• 5HT3
•
Indirectly (more
secondary messages
Bradykinins B1, B2
• Cytokines
• Prostanoids
• Histamine H1
• Serotonin
• 5HT1
•
commonly)
mediating
intracellular
Factors that modify perioperative
pain :
• 1- Site ,nature and duration of surgery.
• 2- Type and extent of incision.
• 3- Physiologic and psychologic makeup of the
patient.
• 4- Pre operative preparation of the patient.
• 5- Presence of complications of surgery.
• 6- Anesthetic management.
• 7- Quality of perioperative care.
• 8- Preoperative treatment of painful stimuli .
Preemptive Analgesia :
• Antinociceptive treatment of that prevents the
establishment of altered central prossesing, which
amplifies postop. Pain.
• Windup:functional changes in the dorsal horn
because of pain .
• This type of therapy ,in addition to reducing acute
pain ,attenuates chronic postop. Pain.
Principles of Pain Management
Anticipate pain
Recognize patient:
• Ask
the patient
• Look for signs (HR, BP, facial grimacing, tears, sweating, etc)
• Find the source
Quantify pain (mild, moderate, severe)
Treat:
Quantify the patients perception of pain
• Correct the cause where possible
• Give appropriate analgesics regularly as required
•
Remember most sedative agents do not provide analgesia
Reassess
Modalities of Pain Relief
 Non-opioid analgesics+opioid analgesics
 Regular injections of opioids
 Continuous IV or SC infusion of opioids
 Patient controlled analgesia (PCA)
 Extradural opioids & or local anesthetics
 Combined exrtadural + spinal analgesia
 Long acting oral opioids
 Long acting regional blocks
 Ketamine (S+)
Modalities of Pain Relief
 Pharmacological
 Non-pharmacological
DRUGS
NSAID’s
COX-1 Minor – Moderate pain
COX-2 rofecoxib, parecoxib-inj Severe pain
Actions:
Inhibit synthesis of PG-E
Direct analgesic effect on higher centers
Modify nociceptive responses-bradykinins
Antiplatelet
Hypothrombinaemia
Lowers body temp
Hypoglycemia
Lower doses
Metabolic
acidosis
only
Adverse gastrointestinal effects
Systemic Opioids :
Analgesic effects of opioids : via receptors in the
CNS.
Roots of administeration :I.M. ,I.V. ,Transdermal
,Oral ,Topical ,I.V. regional ,Perineural ,etc.
I.M. root is the most treatment choice after
surgery.
The” As Needed” part of the order is often
interpreted to mean “As little as possible” .
No relation exists between Gender and opioid
requirement.
Analgesic Opiates
•
•
•
•
•
•
•
Morphine
Pethidine
Fentanyl
Sufentanil
Alfentanil
Remifentani
ANTIDOTE : Naloxone
Routes of administration of
analgesics
Oral
Intravenous
Sublingual/buccal Epidural (opioid)
Oral transmucosal Intrathecal (opiod)
Intranasal
Intra articular (opioid)
Transdermal
Topical - EMLA cream
Rectal
Intradermal
Inhalational
Peripheral N block
Subcutaneous
Nerve plexus block
Intramuscular
Intravenous regional
Modalities of Pain
Relief
 Non-pharmacological
• Transcut. Electrostimulation
• Cryoanalgesia(obselete)
• Acupuncture
• Hypnosis
New Modalities Of Systemic Drug
Administration
The goals of new methods are:
1. Precise,controlled delivery of the prescribed
dose
2. A rapid onset of action
3. Avoidance of first-pass hepatic metabolism
4. Maintenance of a steady-state concentration
of drug
5. An improved side-effect profile and
6. Improved patient compliance
Transdermal Route Advantages
1. Decreased first-pass hepatic
metabolism
2. Decreased gastrointestinal
degradation
3. Stable plasma concentrations,and
4. Improved patient compliance
Treatment methods :
• 1-Systemic opiods.
• 2-Patient-controlled analgesia.
• 3-Regional anesthetic techniques .
• . a : Intraspinal analgesia.
•
b :Patient-controlled epidural analgesia.
•
c :Combined spinal-epidural technique.
•
•
•
•
•
4-intraarticular analgesia.
5-Nonopioid analgesics.
6-Cryoanalgesia.
7-T.E.N.S.
8-Psychologic and other methods.
Patient-Controlled Analgesia:
PCA was originally developed to minimize the effects
of pharmacokinetic and
Pharmacodynamic variability among patients.
A negative feedback loop exists: experiencing
pain>>>Medication demanded>>>Reducing pain
>>>No further demand .
• If Nurses, Relatives,or Parents assume responsibility
for drug administration,or if using this device by the
patient is for reasons other than pain relief ,this loop
fails.
• Cases of respiratory depression during PCA
use have been reported.
• Causes :advanced age, hypovolemia, large
doses, use of background continuous-infusion
mode.
• No difference in respiratory mechanics
between PCA and IM opioids
(FEV1,FRC,PFR)is seen.
Side effects of PCA:
• Nausea ,Vomiting ,Itching.
• Treated by changing opioid or using
drugs that provide symptomatic relief.
• A pre printed set of standard orders
can facilitate a uniform standard of
care.
Regional Anesthetic Techniques:
• Advantages:
• Positive respiratory, cardiovascular and
neuroendocrine
effects;
reduced
thromboembolic complications and blood
loss; and reduced convalescence
IDEAL COMPONENTS
1.
2.
3.
4.
5.
6.
7.
Block SENSORY feeling
Immobilize MOTOR responses
Obtund REFLEXES
wipe out MEMORY
Control VC and CTZ
Not permanent
Cause sense of well-being
REGIONAL ANESTHESIA
SEGMENTAL LOSS OF SENSATION
BY BLOCKING NERVE CONDUCTION
REGIONAL
1. SPINAL
2. EPIDURAL
4. INTRAVENOUS ( BIER )
5. AXILLARY (INFILTRATION)
6. RETROBULBAR
LOCAL ANESTHETICS
•
•
•
•
•
AMIDES
BUPIVACAINE
LIDOCAINE
ROPIVACAINE
MEPIVACAINE
PRILOCAINE
MAX / DOSE
2 MG/KG
7 MG/KG
4 MG/KG
7 MG/KG
6MG/KG
LOCAL ANESTHETICS
ESTERS
CHLOROPROCAINE
COCAINE
NOVOCAINE
TETRACAINE
MAX /DOSE
20 MG/KG
3 MG/KG
12 MG/KG
3 MG/KG
LOCAL ANESTHETICS
Local anesthetics are
the drugs, which
reversibly block the
generation,
propagation and
oscillations of
electrical impulses in
the excitable tissues.
MECHENISM OF ACTION
• Block nerve fiber conduction by acting
directly on nerve membranes to inhibit
sodium ion from crossing the membrane
– Nerves cannot depolarize
– Conduction of impulses is blocked
Mechanism of Action
• Decrease or prevent transient increase in the
permeability of excitable membranes to Na+ ions
• Direct interaction with voltage gated Na+
channels
• Increase in threshold
• Decrease in the rate of rise of A.P.
• Slows down the conduction
Mechanism of Action
• Site of action - Inside the membrane
• Binding sites within the Na+ channel
• Heterotrimeric complexes of glycosylated
proteins ( 300 k Da)
• 3 sub units- a, b1& b 2
• a has I- IV homologous domains
• Each domain has 6 transmembrane domains
• Bind with S6 transmembrane domain.
CONTRAINDICATIONS

RELATIVE
–Patient Appropriateness
–Local Infection near injection site
–Hypovolemia
–CNS Disease
–Chronic Back Pain or Prior Lami
–Prior SAB with difficulty
Nerve Fiber and
Local Anesthetic Setup
Sequence of clinical anesthesia
1. Sympathetic block (vasodilate & skin T0)
2. Loss of pain and temperature sensation
3. Loss of proprioception
4. Loss of touch and pressure sensation
5. Loss of motor function
n
Interscalene brachial plexus blocks :analgesia
for 12-24 hrs.
Sciatic and Femoral n. blocks :similar results.
Intercostal n. blocks : 6-12 hrs. analgesia.
Administration of long acting L.A.s from a
catheter into pleural cavity :unilat. Analgesia
with little or no sensory block.
L.A. infusion into Axillary sheath, Femoral
sheath, and the vicinity of the Sciatic
n.:analgesia and particularly useful to
facilitate
perfusion
after
extensive
revascularization.
L.A. boluses or infusions :
• Advantages over parenteral opioids:
• Early ambulation, improve bowel function,
higher arterial O2 tension, fewer pulmonary
complications.
• For optimal results, the catheter tip should be
near the segments innervating the insicision.
PLUXES BLOCK
BRACHEAL PLUXEX BLOCK
Segmental Level of Block
Required
T-4 to T-6
IntraAbdominal
T-6 to T-8
GU, Low
Abdominal
T-8 to T-10
GU, A/R, Legs
T-4
T-6
T-10
IVRA (BIER’S BLOCK)
SPINAL ANESTHESIA
Intraspinal analgesia:
With:
• Opioids
• Opioid-L.A. mixture
• Ketamine
• Clonidine
• Neostigmine
Opioids:
• Initial reports in 1979.
• Single injection of intrathecal Morphin
provides about 24 hrs. analgesia.
• Epidural root uses more, because:
• Popularity of technique during surgery,
ability to leave catheter in place, familiarity
with technique, no risk of PDPH.
• Elderly patients require remarkably
small doses of epidural morphine.
• Fentanyl is useful when rapid onset
of epidural analgesia is important.
• Epidural meperidine is widely used
in some parts of the world and as
with other opioids, respiratory
depression can occure.
Respiratory depression
• early:
• Delayed:
• Between 6 and 12
• In the first two
hrs.
hrs.
• Consequent of
rostral spread of
• Is the result of
opioid in CSF to
vascular uptake
respiratory center in
and
the floor of 4th.
redistribution.
Ventricle.
• Pruritus is a common side effect and is
seen more in obstetrics patients.
• Face is a common site of itching.
• Although it is not due to histamine
release, antihistamines provide
symptom relief.
• Nalbuphine is also of value.
• Naloxone is consistently effective
(repeated doses or infusion).
• Urinary retention is higher in
volunteers than in patients and in men
than in women.
• Naloxone prevents or reverses it but
may require doses that antagonizes
analgesia.
• Most patients are able to void
spontaneously when the catheters are
removed.
• Nausea and vomiting: due to rostral spread
of opioid in CSF to the vomiting center
and the CTZ .
• Treatment:
• first line: antiemetics (may produce
unwanted sedation and resp. depression ) ,
Scopolamine patches.
• Second line: I.V. droperidol,
Ondansetrone.
• Sedation produced by intraspinal
opioids may be the result of spread of
the drug in CSF to receptors in the
thalamus, limbic system or cortex and
hypercarbia can augment it.
• Epidural buprenorphine 0.15 mg.
produces prolonged depression of the
CO2 response that lasts 8-12 hrs.
Ketamine:
• Produces analgesia via interaction with
cholinergic, adrenergic, and serotonergic
systems.
• Side effects: sedation, blurred vision,
tachycardia, hypertension, and hallucinations.
• In some studies on baboons : neurotoxic
changes.
• The routine use of intrathecal ketamine in
humans is not recommended.
Clonidine:
• If administered by the oral route can
augment spinally mediated opioid
analgesia.
• Epidural or intrathecal clonidine can
provide effective analgesia alone.
• Intrathecal clonidine does not provide
surgical anesthesia.
Intra-Articular analgesia
• Following arthroscopic surgery, a combination
of systemic Ketorolac and intra-articular
bupivacaine decreased analgesic requirement
and pain.
Nitrous oxide:
• Useful, especially for painful experiences of short
duration (dressing changes, debridements).
• Rapid onset of analgesia and rapid recovery.
• In concentrations of 30-50% is as potent as 10 mg.
I.M. morphine.
• “Anesthesia” may occur>>>risk of aspiration.
• Long term administration: causes bone
marrow suppression and leukopenia
(reversible when detected early).
• Entonox:50%mixture of N2O with oxygen.
Cryoanalgesia:
• Temp.s between -5 and -20`causes disintegration of
axons and breakdown of myelin sheaths while the
perinurium and epinurium remain intact.
• Is used most common for thoracotomy pain and
hernia repair pain.
• Residual neuropathic pain has been seen following
cryoanalgesia.
Transcutaneous electrical nerve
stimulation(T.E.N.S.)
• Uses both for chronic pain and acute
perioperative pain.
• Advantages: absence of opioids side effects
(resp. depression, sedation, nausea and
vomiting, urinary retention)
• It is simple, noninvasive and free of toxicity.
• The mechanism of analgesia by TENS is not
known and it may be by:
• Modulation of nociceptive impulses in the
spinal cord (gate control theory).
• Activation of inhibitory area in the brain
stem.
• Stimulation of the release of endorphins, or
a combination of these mechanisms.
• A placebo effect may play a role.
Psychologic and other methods:
• After surgery patients may suffer ”discomfort” due to
headache, NG tubes, drains, IV catheters, or anxiety,
fear, and insomnia.
• Therapy of these problems may result in reporting of
less “pain”.
• Preoperative discussion, reassurance and provision
information results in less anxiety, less opioid use
and shorter hospital stay.
• Relaxation tapes prior to surgery results in
less analgesic use and a smoother recovery.
Perioperative analgesia in special
.
populations
Pediatric patients:
• Misconceptions about pain in children are common
(e.g. children don’t feel pain, or if it is felt it is not
remembered.
• Pain causes suffering and psychologic abnormalities
in children of all age.
• Special scales are available for young children (self
reporting of pain).
• In preverbal children, the interpretation of behavior
must be used to estimate intensity of pain.
• Because of fear of IM injections alternatives are:
sublingual, rectal and transdermal routs.
• I.V. PCA is effective in children.
• Caudal opioid analgesia can be used in children.
• Regional techniques: dorsal nerve block of the
penis, or lidocaine jelly, or EMLA creams for
circumcision, ilioinguinal and iliohypogastric nerve
blocks for pains after orchiopexy and
herniorrhaphy, etc.
• NSAID,s are considered as
adjuncts rather than as primary
agents.
Elderly patients:
• The average age of surgical patients will
increase in the future.
• Older patients have more complex cases than
younger.
• PCA & PCEA is ineffective in some elderly
patients because of their reluctance.
• Treatment of perioperative pain
in elderly remains inadequate
because:
• Fear of complications associated
with treatment of pain.
• Pain is reported less in elderly.
• NSAID,s may have benefits in elderly
because:
• Different site of action that may be more
effective.
• Opioid sparing.
• An additional anti-inflammatory effect.
• But they have increased risk of side effects
because of decreased renal
clearance>>>they doses must be
decreased.
Advantages of regional anesthesia:
•
•
•
•
•
•
•
Minimizing physiologic trespass.
Pharmacologic simplicity.
Reduced blood loss.
Fewer thromboembolic complications.
Reduced stress response.
Less confusion.
Less postoperative pain.
Patients with chronic pain
and /or chronic opioid use
• General principles:
• 1-expect high self-reported pain scores.
• 2-base treatment decision on objective
pain assessment (deep breathing,
coughing, etc.).
• 3-recognize and treat nonnociceptive
sources of suffering.
• Continue opioids for as long as is
appropriate for acute pain.
Addiction:
• A chronic disorder characterized by
compulsive use of a substance resulting in
physical, psychologic, or social harm to the
user and continued use despite that harm.
Clinical triad suggestive of addiction:
• 1-high self-reported pain scores.
• 2-high opioid use compared with other
patients having similar procedures.
• 3-a relative absence of opioid-induced side
effects.
• PCA is not good for providing
basal opioid replacement.
• PCA is good for extra opioids
needed for postoperative pain.
ROLE OF THE
ANESTHESIOLOGIST IN
PERIOPERATIVE PAIN
MANAGEMENT
Anesthesiologists are a logical choice to provide
periop. Pain relief, because they are:
1-familiar with the pharmacology of analgesics and
L.A.s.
2-aware of short- and long-term effects of drugs
given intraoperatively.
3-knowledgeable about pain pathways and their
interruption.
4-are skilled in techniques available to provide
superior pain control.
EPIDURAL ANESTHESIA
EPIDURAL DRUG ADMINISTRATION
FIXATION OF CATHETER
FINAL SKIN FIXATION AND DRESSING
LEST YOU FORGET
Discomfort from:
• Full bladder/bowel/gasses
• Noise
• Alarms
• Visitors
• Painful IV site
• Multiple lines
• Repeated disturbance from medical
personnel
• Complications of analgesic drugs
• Other pathological complications
Reference book and the
relevant page numbers..
Thank You 
Dr.
Date: