Steps of Systematic Research

 

Systematic Research follows certain steps that are logical in order.

These steps are:

1- Understanding the nature of the problem to be studied and identifying the related area of knowledge.

2- Reviewing literature to understand how others have approached or dealt with the problem.

3- Collecting data in an organized and controlled manner so as to arrive at valid decisions.

4- Analyzing data appropriate to the problem.

5- Drawing conclusions and making generalizations.

Characteristics of Research:

Research is a process through which we attempt to achieve systematically and with the support of data the answer to a question, the resolution of a problem, or a greater understanding of a phenomenon.

This process has eight distinct characteristics:

Research…

1. Originates with a question or problem.

2. Requires a clear articulation of a goal.

3. Follows a specific plan of procedure.

4. Usually divides the principal problem into more manageable sub-problems.

5. Is guided by the specific research problem, question, or hypothesis.

6. Accepts certain critical assumptions.

7. Requires the collection and interpretation of data in attempting to resolve the problem that

initiated the research.

8. Is by its nature, cyclical; or more exactly, helical.

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What is the meaning of Research?

 

The word “research” originated from the old French word “researcher” meaning to search and search again.

It literally implies repeating a search for something and implicitly assumes that the earlier search was not exhaustive and complete in the sense that there is still scope for improvement.

Research in common parlance refers to a search for knowledge.

It may be defined as a scientific and systematic search for pertinent information on a specific topic/area. In fact, research is an art of scientific investigation.

The Advanced Learner’s Dictionary of Current English lays down the meaning of research as “a careful investigation or inquiry, especially through search for new facts in any branch of knowledge”. Redman and Mory define research as “a systematized effort to gain new knowledge”. Some people consider research as a movement, a movement from known to unknown. It is actually a voyage of discovery.

Research is a scientific approach to answering a research question, solving a problem, or generating new knowledge through a systematic and orderly collection, organization, and analysis of information with the ultimate goal of making valuable research in decision-making.

Systematic research in any field of inquiry involves three basic operations:

1. Data collection: It refers to observing, measuring, and recording information.

2. Data Analysis: It refers to arranging and organizing the collected data so that we may be able to find out what their significance is and generalize about them.

3. Report writing: It is an inseparable part and a final outcome of a research study. Its purpose is to convey the information contained in it to the readers or audience.

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Anesthetic Considerations for Patients with Liver disease

Preoperative:

1. Assess the Degree of hepatic impairment, Severity, and Hepatic reserve by the Child-Turcotte-Pugh scoring system.

2. AVOID: Premedication, IM injections, Contact with blood or body fluids, unnecessary esophageal instrumentation.

Regional Anesthesia:

-Regional anesthesia might be used when possible in patients with advanced liver disease.

-Coagulopathy (PT & INR) should be considered as a contraindication to some types of regional anesthesia.

-AVOID Epidural a. (Large amounts of amide LAs).

IV Anesthetics:

-Propofol, Ketamine (in hypotensive patients).

Opioids:

-Opioids can also be used successfully in patients with the hepatic disease despite certain pharmacological consequences (decreased clearance and prolonged half-life).

-Fentanyl is considered the opioid of choice because it does not decrease hepatic oxygen and blood supply nor does it prevent increases in hepatic oxygen requirements when used in relatively moderate doses.

-AVOID Morphine (Active metabolite, Prolonged action).

Changed Pharmacokinetics:

-The half-life of lidocaine in patients with liver disease may be increased by more than 300%, for benzodiazepines by more than 100%, etc.

-For drugs binding to albumin, the volume of distribution is decreased and therefore the dose of the drug should be decreased (e.g. sodium pentothal).

Muscle Relaxants:

-Suxamethonium → Prolonged action, Atracurium, Cisatracurium (of choice).

-AVOID Pancuronium, Vecuronium (Hepatic metabolism).

-The volume of distribution of many drugs can be substantially increased (for different reasons, including an increase in gamma globulin and edema), dictating a necessity to increase the first effective dose of the drug.

-However, owing to a decrease in hepatic blood flow and hepatic metabolic and excretory functions, as well as impaired renal function, the clearance of such a drug is decreased, and therefore the effect can be prolonged (e.g. pancuronium).

-Atracurium has a theoretical advantage because its metabolism is not dependent on liver function. Therefore, it is not surprising that the clearance and elimination half-life of atracurium in patients with impaired hepatic and/or renal function is not particularly different from those who have a normal hepato-renal function. However, the volumes of distribution are larger, and, accordingly, the distribution half-lives are shorter in patients with severe hepato-renal dysfunction compared with normal individuals.

-Titration of any relaxant according to the transcutaneous nerve stimulation monitoring is beneficial because the degree of hepatic dysfunction affects the degree of pharmacokinetic disorders.

Inhalational Anesthetics:

-Halothane should be avoided because it leads to the most prominent decrease in hepatic blood flow and oxygen supply and postoperative hepatic dysfunction. In addition, immunologically mediated severe postoperative halothane hepatitis may follow halothane anesthesia.

-Isoflurane seems to be a better choice if an inhalational technique is selected.

-More recently introduced volatile anesthetics, sevoflurane, and desflurane, of them, can be used safely in patients with liver disease, as they preserve hepatic blood flow.

-Nitrous oxide has been used in patients with advanced hepatic disease for many years, and so far has not been incriminated in increased anesthesia-related hepatic postoperative complications. However, a well-known sympathomimetic effect of nitrous oxide and some possibilities of jeopardizing oxygenation render the routine use of nitrous oxide in patients with advanced liver disease undesirable. It is important to remember that long surgical operations under anesthesia with nitrous oxide might result in the accumulation of nitrous oxide in the intestinal lumen with subsequent intestinal distension.

Others:

-Renal function must be maintained by administering proper fluid load (volume and content); (avoid Na+ overload, use glucose-containing solutions for hypoglycemia, albumin 5% is the preferred colloid), and diuretics if needed.

-The parameters of controlled ventilation should be carefully selected to avoid an unnecessary increase in intrathoracic pressure which may impede venous return thereby decreasing cardiac output.

-Monitoring the coagulation state during surgery can be important. The treatment should be based on the results of hematologic monitoring and may include administration of platelets, fresh frozen plasma, cryoprecipitate, and sometimes tranexamic acid.

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 Rheumatoid Arthritis:

A common, autoimmune connective tissue disease, primarily involving joints, but with widespread systemic effects. There is hypergammaglobulinemia, and rheumatoid factors, which are autoantibodies of IgE, IgA, and IgM classes, are present.

Preoperative abnormalities:

1. Articular problems:

-The joint disease involves inflammation, formation of granulation tissue, fibrosis, joint destruction, and deformity. Any joint may be affected. Those of particular concern to the anesthetist is the cervical, the temporomandibular, and the cricoarytenoid joints.

-Airway obstruction can occur from closely adducted, immobile vocal cords, or from laryngeal amyloidosis. Rheumatoid nodules can affect the larynx.

2. Extra-articular problems: occur in more than 50% of patients.

a) Lungs. May be affected by effusions, nodular lesions, diffuse interstitial fibrosis, or Caplan’s syndrome. This is a form of massive pulmonary fibrosis seen in coal miners with rheumatoid arthritis or positive rheumatoid factor, and probably represents an abnormal tissue response to inorganic dust. There may be a restrictive lung defect, with a contribution from reduced chest wall compliance.

b) Kidney. Twenty-five percent of patients eventually die from renal failure. Renal damage may be related to the disease process itself, secondary amyloid disease, or drug treatment.

c) Heart. Is involved in up to 44% of cases. Small pericardial effusions are common but are not usually of clinical significance. Rarely, pericarditis and tamponade may occur, usually in seropositive patients and those with skin nodules. Other problems include endocarditis or left ventricular failure. Occasionally heart valve lesions occur and are of two types; rheumatoid granulomas involving the leaflets and ring, and no granulomatous valvular inflammation with thickening and fibrosis of the leaflets.

d) Blood vessels. A widespread vasculitis can occur. Small arteries and arterioles are often involved, frequently in the presence of relatively disease-free main trunk vessels. Significant ischemia may result, in the actual effects depending on the tissue or organ supplied.

e) Autonomic involvement.

f ) Gastrointestinal. Swallowing problems and dysphagia were found in patients with classical rheumatoid arthritis.

g) Peripheral neuropathy.

3. Chronic anemia, which has been shown to respond to erythropoietin therapy, is common.

Anesthetic problems:

1. Disease of the cervical vertebrae. Cervical involvement, and damage to the cervical spinal cord, have been associated with neck manipulation during anesthesia and sedation. Instability is said to occur in 25% of patients with rheumatoid arthritis. Of these, one-quarter will have no neurological symptoms to alert the physician. The problem of instability is not necessarily confined to those with longstanding diseases.

The commonest lesion is that of atlantoaxial subluxation, although subaxial subluxations may occur in addition. Destruction of bone, and weakening of the ligaments, allow the odontoid peg to migrate backward and upwards, compressing the spinal cord against the posterior arch of the atlas. Thus, the main danger lies in cervical flexion.

The potential dangers of anesthesia and endoscopy have been emphasized. Flexion of the head and reduction in muscle tone may result in cervical cord damage. Dislocation of the odontoid process and spinal cord damage were discovered in a patient undergoing postoperative IPPV in the ITU. It was not known exactly when this had occurred.

2. Cervical instability below the level of a fusion. Those who have previously undergone occipital cervical fusion may develop cervical instability below the level of the original arthrodesis. Occipital-cervical fusion is thought to generate a greater force at the lower cervical level that in turn stresses the unfused facet joints.

3. Laryngeal problems. A constant pattern of laryngeal and tracheal deviation is reported to occur in some patients, particularly those with proximal migration of the odontoid peg. The larynx is tilted forwards, displaced anteriorly and laterally to the left, and the vocal cords are rotated clockwise. Involvement of the larynx in the rheumatoid process is more common than was previously thought. However, fatal airway obstruction occurred following cervical spine fusion, secondary to massive edema in the meso- and hypopharynx.

4. The laryngeal mask airway should not be relied upon to overcome failed tracheal intubation. It was impossible to insert a laryngeal mask airway into a patient with a grade 4 laryngoscopic view. Subsequent cervical X-rays with the head maximally extended showed that the angle between the oral and pharyngeal axes at the back of the tongue was only 70 degrees, compared with 105 degrees in five normal patients. A simulation of different angles using an aluminium plate showed that at an angle less than 90 degrees, the laryngeal mask airway could not be advanced without kinking at the corner.

5. Sleep apneas. Medullary compression associated with a major atlantoaxial subluxation may result in nocturnal oxygen desaturation.

6. Limitation of mouth opening may occur secondary to arthritis of the temporomandibular joints. This is a particular problem in juvenile rheumatoid arthritis.

7. A pericardial effusion and tamponade can be presented as an acute abdominal emergency in patients with seropositive rheumatoid arthritis.

8. Rheumatoid aortic valve involvement may be more rapidly progressive than aortic valve disease from other causes so that there is little time for compensatory hypertrophy of the ventricle to occur. Acute aortic regurgitation caused sudden cardiac failure in a young woman and required urgent valve replacement.

9. Lung disease can result in reduced pulmonary reserve and hypoxia.

10. An increased sensitivity to anesthetic agents may occur.

Management:

1. Clinical assessment of neck and jaw mobility. The Sharp and Purser test gives some indication of cervical spine instability. The patient should be upright, relaxed, and with the neck flexed. With a finger on the spinous process of the axis, the forehead should be pressed backward with the other hand. Normally there is minimal movement. If subluxation is present, the head moves backward as reduction occurs.

2. A lateral view of the cervical spine in flexion and extension will show the distance between the odontoid peg and the posterior border of the anterior arch of the atlas. If subluxation is present, this distance is greater than 3 mm. Frontal views of the odontoid and entire cervical spine have also been suggested.

3. Cervical X-rays of patients who have previously undergone occipital spinal fusions should be carefully examined for evidence of cervical instability at a lower level.

4. Intubation methods. Cervical instability may be an indication of awake fiberoptic intubation with the application of a collar or Crutchfield tongs, to maintain rigidity during surgery. Since spinal instability is usually in flexion, some authors believe that safe tracheal intubation can be achieved under general anesthesia by careful extension of the head, except in the rare instances of posterior atlantoaxial subluxation when fibreoptic intubation is indicated. Emergency control of the airway has been described using a laryngeal mask airway in a patient who developed acute pulmonary edema following occipital-cervical fusion.

5. Deviation of the larynx may make fibreoptic laryngoscopy more difficult in some patients. Examination of the orientation of the larynx by indirect laryngoscopy at preoperative assessment may be helpful. If there is cricoarytenoid involvement, care should be taken with the choice of tracheal tube size and tube insertion. Cricoarytenoid arthritis may occasionally necessitate permanent tracheostomy.

6. Although the use of the laryngeal mask airway is increasingly common, as mentioned above, it cannot always be relied on in patients with severe flexion deformities of the neck.

7. Assessment of pulmonary function and reserve.

8. Examination for other significant complications, such as valvular disease, or pericardial effusion.

9. Extreme caution should be observed if epidural or caudal anesthesia is to be undertaken in patients in whom intubation difficulties are anticipated. Even after a test dose to exclude an accidental spinal, or vascular penetration, the block should only be established very gradually.

10. The use of cervical epidural analgesia for the treatment of digital vasculitis has been reported.

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Laryngeal Mask Airway

Laryngeal Mask Airway (LMA)

1-The LMA-Classic™:

-It is a reusable LMA™ airway for general anesthesia.
-The LMA-Classic™ is available in eight sizes: (1, 1½, 2, 2½, 3, 4, 5, and 6).

Advantages:

-A safe and effective alternative to the endotracheal tube and the facemask.

-Over 100 million uses worldwide.

-Leaves the anesthetist's hands free to attend, to monitoring and record keeping.

-Latex-free and exceptionally well tolerated.

-A reusable device that can be cleaned and steam sterilized up to 40 times before being discarded.

2-LMA-Unique™ (Single-use):

-The LMA-Unique™ is a convenient, single-use LMA™ airway suitable for general anesthesia procedures.

-The LMA-Unique™ is available in sizes: (1, 1½, 2, 2½, 3, 4, and 5).

-The LMA-Unique™ is a disposable, single-use device, made to the same design specifications as the LMA-Classic™.

Advantages:

-Packaged sterile - ready for use.

-Suitable for use on emergency vehicles.

-Suitable where access to sterilization facilities is limited.

-Made of medical-grade PVC.

3-LMA-Flexible™:

-The LMA-Flexible™ is a reinforced LMA™ airway with a flexible airway tube.

-The LMA-Flexible™ is available in sizes: (2, 2½, 3, 4, 5, and 6).

-The LMA-Flexible™ is a re-usable device that can be cleaned and steam sterilized up to 40 times before being discarded.

Advantages:

-Designed for ENT, dental, and head surgery.

-Allows extreme flexion.

-Guaranteed kink and crush-proof.

-Latex-free.

4-LMA Flexible (Single-use):

-The LMA Flexible™ Single Use is ideal for use in ENT, ophthalmic, dental, and other head and neck cases and extends the LMA™ Airway benefits of hemodynamic stability and smoother emergence to more procedures.

5-LMA-ProSeal™:

-The LMA-ProSeal™ is an advanced LMA™ airway suitable for general anesthesia.

-It has a unique double cuff arrangement that provides an exceptionally effective, 'hands-free' airway seal, at low intracuff pressures.

-The LMA-Proseal™ is available in sizes: (1½, 2, 2½, 3, 4, and 5).

-The LMA-Proseal™ is a re-usable device that can be cleaned and steam sterilized up to 40 times before being discarded.

Advantages:

-A new double tube design separates the respiratory and alimentary tracts, providing a safe escape channel for regurgitated fluids in the event of unexpected regurgitation.

-The mask is designed to be a minimally stimulating airway device, whose cuff tip presses against the upper oesophageal sphincter when it is correctly positioned. The sides of the mask face the pyriform fossae and the upper border rests against the base of the tongue.

-Latex-free.

6-LMA Supreme™ (Single-use):

-The first and only single-use laryngeal mask with a built-in drain tube.
-The integrated drain tube is designed to channel fluid and gas safely away from the airway. Several simple and quick tests help verify accurate positioning.
-An improved curve for easy insertion. Subtle refinements in the mask make correct placement easier.

7-LMA Fastrach™ & LMA Fastrach™ ETT:

-The design of the LMA-Fastrach™ facilitates rapid insertion from any position, even if space is limited, and moving the patient is a possible hazard.

-The device is self-positioning with the rigid tube designed to fit the curvature of the palatopharyngeal arch, enabling a firm seal to be achieved.

-The LMA-Fastrach™ is available in sizes: (3, 4, and 5).

-The LMA-Fastrach™ is a reusable device that can be cleaned and steam sterilized up to 40 times before being discarded.

Advantages:

The LMA-Fastrach™ has additional features to those of the LMA-Classic™:

-Designed specifically for the anatomically difficult airway.

-Ideal in emergency situations.

-Can be used as an intubating tool, with no interruption of patient oxygenation.

-Allows insertion in the neutral position, in limited space.

-No need to move the patient.

-No need to insert fingers into the patient's mouth.

8-LMA Fastrach™ & LMA Fastrach™ ETT (Single-use):

9-LMA CTrach™:

-The only difficult airway device that allows ventilation, visualization, and intubation.

-The LMA CTrach™ is designed to increase intubation success rates in difficult airways. The LMA CTrach™ mask enables ventilation during intubation attempts while built-in fiber optics provide a direct view of the larynx and real-time visualization of the ET tube passing through the vocal cords.

-The LMA CTrach™ can be inserted exactly the same as the LMA Fastrach™, however, unlike the LMA Fastrach™, once the airway is secured and the patient is being ventilated, the viewer is switched on, placed in the magnetic connector, and a clear image of the larynx is displayed in real-time. The ET tube can be viewed as it enters the trachea. Once the patient is intubated, the viewer is removed and the mask is removed leaving the ET tube in place.

10-i-gel™:

-The i-gel supraglottic airway device accurately and naturally positions itself over the laryngeal framework to provide a reliable peri-laryngeal seal without the need for an inflatable cuff.

-i-gel is made from a medical-grade thermoplastic elastomer, i-gel has been designed to create a non-inflatable, anatomical seal of the pharyngeal, laryngeal, and peri-laryngeal structures whilst avoiding compression trauma.

-i-gel is currently available in sizes: (1, 1½, 2, 2½, 3, 4, and 5), and is supplied in an innovative, color-coded polypropylene ‘cage pack’.

Advantages:

-No inflatable cuff offers easy, rapid insertion.

-An integral bite block reduces the possibility of airway occlusion.

-A buccal cavity stabilizer aids rapid insertion and eliminates potential rotation.

-Made from a unique, soft, gel-like material to allow ease of insertion and reduced trauma.

-Gastric channel designed to improve and enhance patient safety.

-Reduces the possibility of epiglottis downfolding and obstructing the airway.

-Unique packaging protects the i-gel in transit and ensures that it maintains its anatomical shape.

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 Ventilators

-Early ventilators consisted of the generation of negative pressure around the whole of the patient’s body except the head and neck; these were called Cabinet or Iron lung ventilators.

-A negative pressure could also be applied over the thorax and abdomen: Cuirass Ventilators.

Classification:

1. Pattern of gas flow during inspiration:

a) Pressure generators:

Constant pressure is produced by bellows or a moderate weight which produces a decreasing inspiratory flow which alters with changes in lung compliance

b) Flow generators:

Constant flow is produced by a piston, heavyweight, or compressed gas. Flow is unaltered by changes in lung compliance although pressures will vary. These ventilators have a high internal resistance to protect the patient from high working pressures.

2. Power:

Pressure generators are low powered whereas flow generators are high powered.

3. Cycling:

Change from inspiration to expiration may be determined by:

a) Time:

Most common method. The duration of inspiration is predetermined, with the constant flow it may be necessary to preset a Tv; when this has been delivered there is an inspiratory pause (improves distribution) before the inspiratory cycle ends.

b) Pressure:

Used as a pressure limit on other modes. Ventilator cycles into expiration when preset airway pressure is reached (delivers a different Tv if compliance or resistance changes). Inspiratory time varies according to compliance and resistance.

c) Volume:

Usually used with an inspiratory flow restrictor. Cycles into expiration whenever a preset Tv is reached.

d) Flow:

Older ventilators.

4. Sophistication:

Newer ventilators can function in many of the above modes, and also have weaning modes such as SIMV, PS, and CPAP.

5. Function:

a) Minute volume dividers:

Fresh gas flow powers the ventilator. Minute volume equals the FGF divided into pre-set tidal volumes, thus determining the frequency.

b) Bag squeezers:

Replaces the hand ventilation of a Mapleson D or circle system. It needs an external power source.

c) Lightweight portable:

Powered by compressed gas and consists of the control unit and patient valve.

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Charcot-Marie-Tooth Disease

Charcot-Marie-Tooth Disease (CMT)

-Charcot-Marie-Tooth disease (CMT) is a neuromuscular disorder characterized by length-dependent degeneration of the motor and sensory nerve fibers, with a prevalence of 1 in 2,500 (about 200,000 patients in the European Union).

-Anesthesia is administered to this population more frequently than to normal people, as CMT patients often need orthopedic surgery to correct muscle imbalance and limb deformities, and for osteosynthesis of bone fractures as they are prone to falls.

Anesthetic Management Complications:

1-Malignant hyperthermia.

2-Prolonged responses to neuromuscular blocking drugs.

3-Drug toxicity is caused by inappropriate doses in case of severe muscle wasting.

4-Medication-induced exacerbation of neuropathy.

5-Associated deformities such as scoliosis.

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IV Fluids

A) Crystalloid solutions (< 30 000 Dalton):

1-Hypotonic solutions:

- D₅W, ½ NS, D5 ¼ NS, D5 ½ NS.

2-Isotonic solutions:

- NS, Ringer’s, Lactated Ringer’s (Hartmann’s), Ringer’s acetate.

3-Hypertonic solutions:

- NaCl (3%, 7.5%), Mannitol (10%, 20%), NaHCO₃ (5%, 7.5%, 8.4%).

B) Colloid solutions (> 30 000 Dalton):

1-Blood derived:

- Human albumin (5%, 25%).

- Plasma protein fraction 5%.

2-Synthetic:

a) Dextrose Starches:

- They are D-glucose polymers linked by alpha bonds into linear macromolecules prepared from sucrose.

- Their half-life is 12 hours.

- 6% Dextran-70 (Macrodex) MW = 70 000 Dalton

- 10% Dextran-40 (Rheomacrodex) MW = 40 000 Dalton

- Dextran-1 (Promit).

- Dose: 20 ml/kg/d., Max.: 1.5 L/d.

Disadvantages:

- Interfere with blood typing.

- Antiplatelet effect.

- Antigenic effect with anaphylactoid and anaphylactic reactions.

- Affect renal functions and can be associated with renal failure.

b) Gelatins:

- Their M.W. 30 000-35 000 Dalton.

- Their half-life is 4-5 hours.

- Succinylated Gelatin (Gelofusine 3.5%, 4%).

- Polygelline (Hemaccel 3.5%, Hemagel 4%).

- Dose: 20 ml/kg/d., Max.: 1.5 L/d.

Advantages:

- Does not interfere with blood grouping.

- Does not affect renal function.

Disadvantages:

- Histamine-mediated allergic reaction.

c) Hydroxy-Ethyl Starch (HES) (Etherified Starch):

Synthetic colloids resemble glycogen structurally, synthesized from amylopectin.

- Heta-starch (Hexa-starch) (e.g. HAES-Steril, Hespan): M.W. 450 000 Dalton, half-life 48 hours.

- Hextend: M.W. is higher, and the half-life is longer.

- Penta-starch: M.W. 200 000, half-life less than 24 hours.

- Tetra-starch: (e.g. Tetraspan, Voluven): M.W. 130 000, half-life less than 6 hours.

- Dose: 20-50 ml/kg/d.

Advantages:

- Do not affect the coagulation study.

- Not antigenic but can cause anaphylactoid reactions.

- Less expensive than human albumin.

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Ovarian Hyperstimulation Syndrome (OHSS)

- It is a complication of some forms of fertility medication. Most cases are mild, but small proportions are severe.

Causative Medications:

- Associated with the injection of a hormone called human chorionic gonadotropin (hCG) which is used for inducing final oocyte maturation and/or triggering oocyte release.

- The risk is further increased by multiple doses of hCG after ovulation and if the procedure results in pregnancy.

- Using a gonadotropin-releasing hormone (GnRH) agonist instead of hCG for inducing final oocyte maturation and/or release results in an elimination of the risk of OHSS, but a slight decrease of the delivery rate of approximately 6%.

Epidemiology:

- Sporadic OHSS is very rare and may have a genetic component.

- Clomifene citrate therapy can occasionally lead to OHSS, but the vast majority of cases develop after the use of gonadotropin therapy (with the administration of FSH), (Menopur, Pergonal, Repronex) and administration of hCG to induce final oocyte maturation and/or trigger oocyte release, often in conjunction with in vitro fertilization (IVF).

- The frequency varies and depends on patient factors, management, and methods of surveillance. About 5% of treated patients may encounter moderate to severe OHSS.

- Mortality is low, but several fatal cases have been reported.

Risk Factors:

- Risk factors include young age, the development of many ovarian follicles under-stimulation, extremely elevated serum estradiol concentrations, the use of hCG for final oocyte maturation and/or release, the continued use of hCG for luteal support, and the occurrence of a pregnancy (resulting in hCG production).

Pathophysiology:

- OHSS has been characterized by the presence of multiple luteinized cysts within the ovaries leading to ovarian enlargement and secondary complications.

- The central feature of clinically significant OHSS is the development of vascular hyperpermeability and the resulting shift of fluids into the third space.

- As hCG causes the ovary to undergo extensive luteinization, large amounts of estrogens, progesterone, and local cytokines are released. It is almost certain that vascular endothelial growth factor (VEGF) is a key substance that induces vascular hyperpermeability, making local capillaries "leaky", leading to a shift of fluids from the intravascular system to the abdominal and pleural cavity.

- Supraphysiologic production of VEGF from many follicles under the prolonged effect of hCG appears to be the specific key process underlying OHSS. Thus, while the patient accumulates fluid in the third space, primarily in the form of ascites, she actually becomes hypovolemic and is at risk for respiratory, circulatory, and renal problems. Patients who are pregnant sustain the ovarian luteinization process through the production of hCG.

- Avoiding OHSS typically requires interrupting the pathological sequence, such as avoiding the use of hCG. One alternative is to use a GnRH agonist instead of hCG.

Classification:

Mild OHSS:

- The ovaries are enlarged (5–12 cm), slight weight gain, mild abdominal distension, abdominal pain, nausea, diarrhea, and there may be an accumulation of ascites.

Moderate OHSS:

- Excessive weight gain (> 2 pounds/day or > 1 kg/day), increased abdominal girth, vomiting, darker urine and oliguria, excessive thirst, and dry skin and/or hair (in addition to mild symptoms).

Severe OHSS:

- Marked abdominal distention, lower abdominal pains, darker urine or anuria, pleural effusion, respiratory distress, calf and chest pains. There may be hemoconcentration, and thrombosis (in addition to mild and moderate symptoms).

- Symptoms generally resolve in 1 to 2 weeks but will be more severe and persist longer if pregnancy occurs. This is due to hCG from the pregnancy acting on the corpus luteum in the ovaries in sustaining the pregnancy before the placenta has fully developed. Typically, even in severe OHSS with a developing pregnancy, the duration does not exceed the first trimester.

- Early OHSS develops before pregnancy testing and late OHSS is seen in early pregnancy.

Criteria for Severe OHSS:

- Enlarged ovary, ascites.
- Hematocrit > 45%, WBC > 15,000/microliter.

- Oliguria, creatinine 1.0-1.5 mg/dL, creatinine clearance > 50 ml/min.

- Liver dysfunction, anasarca (extreme generalized edema).

Critical OHSS:

- Enlarged ovary, tense ascites with hydrothorax and pericardial effusion.

- Hematocrit > 55%, WBC > 25,000/microliter.

- Oligoanuria, creatinine > 1.6 mg/dL, creatinine clearance < 50 mL/min.

- Renal failure, thromboembolic phenomena (DVT, PE), ARDS.

Complications:

- Ovarian torsion, ovarian rupture, thrombophlebitis, and renal insufficiency.

Prevention:

- Physicians can reduce the risk of OHSS by monitoring FSH therapy, and by withholding hCG medication.

- Regarding dopamine agonists as prophylaxis, a systematic review and meta-analysis concluded that prophylactic treatment with Cabergoline (Dostinex) reduces the incidence, but not the severity of OHSS, without compromising pregnancy outcomes.

- OHSS may also be prevented by coasting, which is ovarian hyperstimulation in IVF without hCG administration for final maturation of follicles.

Treatment:

Mild OHSS:

- Can be treated conservatively with monitoring of abdominal girth, weight, and discomfort on an outpatient basis until either conception or menstruation occurs. Conception can cause mild OHSS to worsen in severity.

Moderate OHSS:

- Is treated with bed rest, fluids (IV hydration), and close monitoring of labs such as electrolytes (hyponatremia, hyperkalemia, acidosis), blood counts, and coagulation profile (PT, aPTT, INR). Ultrasound may be used to monitor the size of ovarian follicles. Depending on the situation, a physician may closely monitor a patient's fluid intake and output on an outpatient basis, looking for an increased discrepancy in fluid balance (over 1-liter discrepancy is cause for concern). Resolution of the syndrome is measured by decreasing the size of the follicular cysts on 2 consecutive ultrasounds.

Severe OHSS:

- Aspiration of accumulated fluid (ascites) from the abdominal (paracentesis) / pleural cavity may be necessary, intercostal tube, as well as opioids for the pain.

- If the OHSS develops within an IVF protocol, it can be prudent to postpone the transfer of the pre-embryos since the establishment of pregnancy can lengthen the recovery time or contribute to a more severe course. 

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