STANDARD OPERATING PROCEDURE FOR OBSERVATION OF CLINICAL SIGNS IN THE LABORATORY ANIMALS

1.0 OBJECTIVE: To design a Standard Operating Procedure that describes the procedure for       

            observation of the clinical signs in the Laboratory Animals.           

2.0 RESPONSIBILITY: It is the responsibility of Veterinarian, Animal House In-charge and Animals Care Personals.

3.0  PURPOSE & SCOPE:

3.1  To outline the method of observation and recording of various clinical signs/symptoms in the test system.

3.2  It is used while recording daily observation and veterinary/physical examination of laboratory animals.

3.3  Observation of animals comprises a visual check on the condition of each animal in the animal house.

3.4  Each animal on experiment must be observed on a minimum two occasions per day for mortality and morbidity.

3.5  In addition, during experiment involving active dosing, all animals must be observed immediately after some time dosing. If severe clinical signs are observed in the animals, more frequent monitoring may be required.

3.6  Observation procedure:

3.6.1       Ascertain from the study schedule and/or protocol, the time of observation and whether anything in particular should be investigated.

3.6.2       Within an animal room observation must be made systematically completing the examination of one cage at a time. If necessary slide each cage forward on the rack sufficiently far too allowed visual inspection of the animals. Assess carefully the state of being of each animal.

3.6.3     If there is any doubt about the condition of an animal remove it from the cage and place it upon a flat, smooth surface free from obstruction. Further

          observe the animal for any lesion or abnormality in appearance, behavior or fur.

3.6.4       If animal is found in extremis prior to next observation period the study director must be consulted to decide whether animal should be painlessly killed (euthanasia/moribund sacrifice).

3.6.5       Any clinical sign observed must be recorded in standard format and/or in daily observation record sheet. The clinical symptoms should be recorded directly as listed or using a code specified in the table.

3.7  Assessing clinical signs:

3.7.1       To assess the possibility of clinical signs, assign value to various observations of animal condition and behavior. Based on observations, a score is assigned to each variable 0- Normal, 1- Mild, 2- Moderate and 3- Severe.

VARIABLE
BODY WEIGHT CHANGE
0	Normal
1	<10 percent weight loss
2	10-15 percent weight loss
3	>20 percent weight loss
PHYSICAL APPEARANCE
0	Normal
1	Lack of grooming
2	Rough coat, nasal/ocular discharge
3	Very rough coat, abnormal posture, enlarged pupils
MEASURABLE CLINICAL SIGNS
0	Normal
1	Small changes of potential significant
2	Temperature change of 1-2 °C, cardiac and respiratory rates increased upto 30 percent
3	Temperature change of >2 °C, cardiac and respiratory rats increased upto 50 percent, or markedly reduced

UNPROVOKED BEHAVIOR
0	Normal
1	Minor changes
2	Abnormal, reduced mobility, decreased alertness, inactive
3	Unsolicited vocalizations, self-mutilation, either very restless or immobile.
BEHAVIOR RESPONSE TO EXTERNAL STIMULI
0	Normal
1	Minor depression/exaggeration of response
2	Moderately abnormal responses
3	Violent reaction, or comatose

 

Clinical sign/Symptom code	Clinical sign/Symptom	Clinical sign/Symptom code	Clinical sign/Symptom
1	Normal	21	Orchitis
2	Found Dead	22	Abscess
3	Moribund state	23	Abrasion
4	Cannibalism	24	Fissuring
5	Emaciation	25	Pruritis
6	Obesity	26	Ulcer
7	Hyperactivity	27	Sloughing
8	Aggression	28	Swelling
9	Lethargy	29	Ascites
10	Catalepsy	30	Iritis
11	Abnormal gait	31	Dysentery
12	Ataxia	32	Constipation
13	Retropulsion	33	Vocalization
14	Microphthalmos	34	Edema
15	Anophthalmos	35	Erythema
16	Hyperesthesia	36	Erythematic eruption

 

17	Hypoaesthesia	37	Alopecia
18	Tachycardia	38	Sweating
19	Bradycardia	39	Salivation
20	Emesis (Vomiting)	40	Tachypnoea
41	Wry neck (Torticolis)	71	Nasal discharge
42	Dermatitis	72	Snuffle
43	Vesicle	73	Lacrimation
44	Papule	74	Chromodacryorrhoea
45	Scale	75	Miosis
46	Ring tail	76	Mydriasis
47	Mass formation	77	Exophthalmos
48	Tail erection (straub tail)	78	Ptosis
49	Abortion	79	Cataract
50	Epitaxis	80	Corneal opacity
51	Weakness	81	Conjunctivitis
52	Injury (wound)	82	Chemosis
53	Spastic locomotion	83	Diarrhea
54	Hopping gait	84	Prolapse
55	Rolling gait	85	Polyurea
56	Waddling gait	86	Piloerection
57	Prostration	87	Anuria
58	Tremors	88	Dysurea
59	Fasciculation	89	Pyurea
60	Clonic convulsion	90	Incontinence
61	Tonic-Clonic convulsion	91	Writhing
62	Convulsion (Seizures)	92	Weight loss
63	Opisthotonos	93	Anorexia
64	Paralysis	94	Hyperthermia
65	Spastic paralysis	95	Hypothermia

66	Flaccid paralysis	96	Haematuria
67	Abdominal breathing	97	Haemorrhage
68	Dyspnoea	98
69	Gasping
70	Cyanosis

4.0  DEFINITIONS:

4.1  Normal- Healthy, normal physical and mental condition, free from disease.

4.2  Found Dead- The cessation of all vital function in a living organism.

4.3  Moribund State- A diagnosis and decision point based on appropriate clinical judgment, taking into account the severity of condition, the amount of pain and distress, the prognosis and the potential loss of valuable data at which time the animal is dammed to be dying with quality of life already significantly impaired and humane killing becomes unavoidable at this point.

4.4  Cannibalism- The practice of eating the flesh of its own species.

4.5  Emaciation- The state of extreme leanness /loss of the subcutaneous fat.

4.6  Obesity- Condition characterized by excessive movement/activity.

4.7  Hyperactivity- General restless or destructive behavior.

4.8  Aggression- Hostile, injurious or destructive behavior.

4.9  Lethargy- A state of excessive fatigue/sluggishness.

4.10         Catalepsy- Animal tends to remain in any position it is placed in.

4.11         Abnormal gait- The abnormal appearance of animal while it is moving.

4.12         Ataxia- Inability to control and coordinate movement while animal is walking.

4.13        Retropulsion- Persistent backward locomotion or forceful, sudden backward movement.

4.14         Microphthalmos- Abnormally small eye ball.

4.15         Anophthalmos- Complete absence of eyes.

4.16         Hyper aesthesia- Increased sensitivity to sensory stimuli such as pain or touch.

4.17         Hypoaesthesia- Decreased sensitivity to sensory stimuli particularly touch.

4.18         Tachycardia- An abnormally rapid heart rate.

4.19         Bradycardia- An abnormally slow heart rate.

4.20         Orchitis- Inflammation of the testicles.

4.21         Abscess- Localized collection of pus in any part of the body.

4.22         Abrasion- Wound in which the superficial layer of skin (epidermis) is removed.

4.23         Fissuring- It is characterized by a crack or cleft in the skin.

4.24         Pruritis- Localized or generalized itching due to irritation of sensory nerve ending.

4.25         Ulcer- It is a wound, which does not tend to heal.

4.26         Sloughing- Layer or mass of dead tissue separated from surrounding living tissue.

4.27    Swelling- An abnormal enlargement of a part of the body. Swelling can be due to an abscess, haematoma, inflammation, tumor etc.

4.28         Ascites-An accumulation of watery fluid in the peritoneal cavity.

4.29         Iritis- Inflammation of iris manifested by vascular congestion.

4.30         Dysentery- Frequent watery stools with blood and mucus.

4.31         Constipation- Difficult or infrequent passage of faeces.

4.32         Vocalization-Spontaneous/unprovoked sound produced by animal due to pain/distress.

4.33         Edema- Abnormal accumulation of fluid in a tissue or cavity.

4.34         Erythema-Abnormal redness of the skin.

4.35         Erythemia eruption- Abnormal redness along with cutaneous elevation of the skin.

4.36         Alopecia- Absence or loss of hair form skin areas where it is normally found.

4.37         Sweating- Excessive secretion of sweat gland.

4.38         Salivation- Excessive secretion of salivary gland.

4.39         Emesis (Vomiting)- Expulsive of the content of the stomach through the mouth.

4.40         Wry Neck (Torticolis)- Twisting of neck with an unnatural position of the head, circling when suspended upside down.

4.41         Dermatis- Inflammation of skin.

4.42   Vesicle- A circumscribed (confined) elevation of skin, less than 0.5cm in diameter containing clear fluid.

4.43         Papule- A small, circumscribed, solid elevated lesion of the skin.

4.44         Scale- Excessive accumulation of discarded keratinous debris over skin surface.

4.45    Ring tail- Annular constriction, subsequent edema, necrosis and sloughing of tail observed generally in unweaned rats.

4.46         Mass formation- An abnormal mass of tissue that may cause swelling on the body surface.

4.47         Tail erection (Straub tail)- The tail is stiff and held in a vertical position for a prolong period.

4.48         Abortion- Expulsion of a dead fetus prior to the normal gestation period.

4.49         Epitaxis- Bleeding from nose.

4.50         Weakness- Loss of physical strength or vigor.

4.51         Injury- The break in the continuity of the skin and soft tissue.

4.52         Spastic locomotion- The legs are stiff and advance slowly by dragging of feet.

4.53         Hopping gait- To move with light bounding skips or leaps (Jumping)

4.54         Rolling gait- To move forward along a surface by revolving on an axis or by repeatedly turning over.

4.55         Waddling gait- To walk with short steps that tilt the body from side to side.

4.56         Prostration- Immobile and rest on belly.

4.57         Tremor- Continuous repetitive twitching (contraction) of skeletal muscle which is usually visible and palpable. The movements are rhythmic and oscillatory.

4.58         Fasciculation- Involuntary twitching/movement of muscles seen on back, shoulder hind limb and digit of the paw.

4.59         Clonic convulsion- Convulsion marked by muscular rigidity and then relaxation.

4.60         Tonic convulsion- Convulsion marked by a persistent firm and violent muscular contraction.

4.61         Tonic-Clonic convulsion- Both type may appear consecutively.

4.62         Convulsion (Seizures)- Powerful involuntary contraction (altering with relaxation) of muscles producing aimless movement and contraction of body.

4.63         Opisthotonos- Condition of spasm of the muscles of the back causing the head and lower limbs to bend forward and trunk to arch forward.

4.64         Paralysis- Complete or partial loss of motor or sensory functions.

4.65         Spastic paralysis- Paralysis with increased muscular tone.

4.66         Flaccid paralysis- Paralysis with loss of muscular tone.

4.67         Abdominal breathing- Breathing by diaphragm, greater deflection of abdomen upon inspiration.

4.68         Dyspnoea- Abnormally difficult or labored breathing.

4.69         Gasping- Convulsive catching of breath with wide open mouth.

4.70         Cyanosis- Bluish discoloration of skin and mucous membrane.

4.71         Tachypnoea- Quick and usually shallow respiration

4.72         Nasal discharge- Discharge from nose.

4.73         Snuffle- Respiratory noise produced by mucosal swelling or accumulation of exudates.

4.74         Lacrimation- The excessive secretion of lacrimal gland.

4.75         Chromodacryorrhoea- Red tears. The eyelids may be smeared with red pigment/porphyrin.

4.76         Miosis- Contraction of pupils regardless of presence or absence of light.

4.77         Mydriasis- Dilation of pupils regardless of presence or absence of light.

4.78         Exophthalmos- abnormal protrusion of eye ball.

4.79         Ptosis- Dropping of upper eye lid.

4.80         Cataract- Opacity of lens.

4.81         Corneal opacity- An opaque spot or area on cornea.

4.82         Conjunctivitis- Inflammation of mucous membrane of conjunctiva.

4.83         Chemosis- Edema or swelling of the conjunctiva around the cornea.

4.84         Prolapse- Protrusion or descent of an organ or part of it from its normal location.

4.85         Diarrrhoea- Abnormal frequent passage of loss of stools.

4.86         Polyuria- Excessive secretion and discharge of urine.

4.87         Piloerection- Contraction of erectile tissue of hair follicle resulting in rough hair.

4.88         Anuria- Absence of urinary secretion.

4.89         Dysurea- Difficult or painful urination.

4.90         Pyuria- Pus in the urine.

4.91         Incontinence- Constant dribbling of urine due to less voluntary control over urination.

4.92         Writhing- Twisting, squiring, contorted motion and often indicate pain or distress.

4.93         Weight loss- Abrupt, significant reduction in body weight.

4.94         Anorexia- Loss of appetite.

4.95         Hyperthermia- Increased in the body temperature.

4.96         Hypothermia- Decrease in body temperature.

4.97         Haematuria- Blood in the urine.

4.98         Haemorrhage- An escape of blood from the blood vessels.

5.0  PROCEDURE:

5.1  The animals were checked every day for any illness or injury.

5.2   The animal care personnel accompanied with Veterinarian gave a thorough check up to the animals.

5.3  In case of any clinical symptom, immediate action was taken.

6.0  PRECAUTIONS:

6.1  The animals should never be left unattended.

6.2  Regular check-up of the animals should be done from time to time.

6.3  The animals should be thoroughly checked for any symptom which could be alarming or harming.

7.0  REFERENCES:

7.1  Klement P, del Nido PJ, Mickleborough L, MacKay C, Klement G, Wilson GJ. Techniques and postoperative management for successful cardiopulmonary bypass and open-heart surgery in dogs. JAVMA. 1987;190:869–874. [PubMed]

7.2  Kohn DF, Martin TE, Foley PL, Morris TH, Swindle MM, Vogler GA, Wixson SK. Public statement: Guidelines for the assessment and management of pain in rodents and rabbits. JAALAS. 2007;46:97–108.[PubMed]

7.3  Kona-Boun JJ, Silim A, Troncy E. Immunologic aspects of veterinary anesthesia and analgesia. JAVMA.2005;226:355–363. [PubMed]

7.4  Kuhlman SM. Principles of anesthesia monitoring: Introduction. J Invest Surg. 2008;21:161–162.

7.5  Landi MS, Kreider JW, Lang CM, Bullock LP. Effects of shipping on the immune function in mice. Am J Vet Res. 1982;43:1654–1657. [PubMed]

END OF THE DOCUMENT

You may like to read these links: 

1. List of In-vivo laboratory Vendors (Capex)

2. List of SOPs and Documents for CPCSEA

3. List of All SOPs and Documents for Laboratory Instruments and Equipment

4. List of All SOPs and Documents for Animal House Facility

5. List of All SOPs and Documents for In-vivo Laboratory