Table of contents :

• dietary supplements
• rehydration therapy / fluid resuscitation : the restoration of water or of fluid content to a body or to a substance which has become dehydrated
• oral rehydration therapy (ORT) / oral rehydration salts (ORS) : oral administration of a solution of electrolytes and carbohydrates in the treatment of dehydration

	WHO	ESPGHAN	Dicrodrol 60®	Reidrax®	GES 60®	Sodioral®
osmolarity	330	200-250	221	225	270	215
glucose	110	74-111	90	75	111	88
Na	90	60	60	60	60	60
K	20	20	20	20	20	20
Cl	80	> 25	37	60	50	30
HCO3-citrate	30	20	14.3	10	30	17
kCal/L	80	55-80	66	54	80	64

• parenteral physiologic solutions
• multiple electrolytes injection
• multiple electrolytes injection type 1 : sodium, potassium, magnesium, chloride (may also contain acetate, acetate and gluconate, or acetate, gluconate, and phosphate)
• multiple electrolytes injection type 2 : sodium, potassium, magnesium, chloride (may also contain either acetate and citrate or acetate and lactate)
• multiple electrolytes and dextrose injection type 1 : dextrose, sodium, potassium, magnesium, calcium, chloride (may also contain acetate, acetate and gluconate, acetate and phosphate, phosphate and lactate, or phosphate and sulfate)
• multiple electrolytes and dextrose injection type 2 : dextrose, sodium, potassium, magnesium, chloride (may also contain acetate, acetate and citrate, acetate and lactate, or gluconate and sulfate)
• multiple electrolytes and dextrose injection type 3 : dextrose, sodium, potassium, chloride (may also contain ammonium, acetate and phosphate, or phosphate and lactate)
• multiple electrolytes and dextrose injection type 4 : dextrose, sodium, magnesium, calcium, chloride, gluconate, sulfate
• multiple electrolytes and invert sugar injection type 1 : equal amounts of dextrose and sucrose*, sodium, potassium, magnesium, chloride, phosphate, lactate
• multiple electrolytes and invert sugar injection type 2  : equal amounts of dextrose and sucrose*, sodium, potassium, magnesium, calcium, chloride, lactate
• multiple electrolytes and invert sugar injection type 3 : equal amonts of dextrose and sucrose*, sodium, potassium, chloride, ammonium
* = or an equivalent solution produced by hydrolysis of sucrose.
• amphoteric electrolyte / ampholyte : a compound containing at least one group that can act as a base and at least one that can act as an acid
• colloidal electrolyte : an electrolyte in which one or more of the ionic components is of macromolecular dimensions.

	Na+ (mEq/L)	K+ (mEq/L)	Cl- (mEq/L)	Ca2+ (mEq/L)	lactate (mEq/L) (used instead of Cl- to maintain electroneutrality : it is converted to HCO3- by hepatic metabolism)	glucose (g/L)
normal (0.9%) saline (NS) :  0.45 g / 50 mL 0.9 g / 100 mL 4.5 g / 500 mL	154	0	154	0	0	0
dextrose 5% in water (D5W)	0	0	0	0	0	50
D5W 2 NS	77	0	77	0	0	50
2.3 D5W 1.3 NS	50	0	50	0	0	33
lactated Ringer's	130	4	109	3	28	0

Maintenance water requirements :
• first 10 kg of weight : 4 mL/kg/h = 100 mL/kg/day
• second 10 kg of weight : 2 mL/kg/h = 50 mL/kg/day
• each kilogram above 20 kg : 1 mL/kg/h = 20 mL/kg/day
Volume of distribution : a dilution method for determining the volume of fluids, e.g., plasma, in a body fluid compartment. A solute (e.g., inulin) is injected into the compartment and, after it is equally distributed, a sample is taken. Then the quantity of solute removed (as by metabolism, excretion, etc.) is subtracted from the quantity administered, and the result is divided by the concentration per milliliter in the sample.
Expected plasma volume increase = (infused volume ^. normal plasma volume) / distribution volume
Infused volume = (expected plasma volume increase ^. distribution volume) / normal plasma volume
Perioperatory fluid management :
• preexisting deficiencies
• approximate quantity of intraoperatory blood loss
• evaporation (duration of operation)
• third space losses
• maintenance requirements
• every type of current loss
20 drops from defluxors = 1 ml (varying according to arm movements)
• hemotherapy / hematherapy / hematotherapy : treatment of disease by the administration of blood or blood products, such as blood plasma
• blood or plasma substitute : a fluid which may be used instead of whole blood or plasma for replacement of circulating fluid in the body
• fresh frozen plasma (FFP) : plasma separated from whole blood and frozen within 8 hours; it contains all coagulation factors including the labile factor V and factor VIII.
• normal human plasma : sterile plasma obtained by pooling approximately equal amounts of the liquid portion of citrated whole blood from > 8 adult humans, used as a blood volume replenisher.
• antihemophilic human plasma : normal human plasma that has been processed promptly to preserve the antihemophilic properties of the original blood; used for temporary correction of bleeding tendency in hemophilias.
• pooled plasma : a mixture of plasma from several donors.
• salt plasma : blood plasma to which a neutral salt has been added to prevent clotting, such as ...
• oxalate plasma : blood plasma to which ammonium oxalate has been added, formerly used to prevent clotting.
• citrated plasma : blood plasma treated with sodium citrate, which prevents clotting.
• true plasma : blood plasma drawn directly from the blood without any change in its gas content.
• plasma volume expander / artificial plasma extender : a substance that can be transfused to maintain fluid volume of the blood in an emergency, supplemental to the use of whole blood and plasma
• special intravenous gelatin solution : a 5 or 6% sterile, pyrogen-free solution of gelatin in isotonic sodium chloride solution
• colloid : a substance comprising very small, insoluble particles, usually 1 to 1000 nm in diameter, that are uniformly dispersed or suspended in a finely divided state throughout a continuous dispersion medium, not settling readily; either phase can be solid, liquid, or gas. The particles are often called the dispersed phase and the dispersion medium the continuous phase. Colloid can refer specifically to the particles or to the system of particles plus dispersion medium.
• antimony trisulfide colloid : antimony sulfide (Sb₂S₃), a pharmaceutic aid.
• association colloid : a colloid in which the dispersed particles are each made up of many molecules.
• dispersion colloid : sometimes specifically an unstable colloid system.
• reversible or stable colloid : a colloid that can be dispersed after having been precipitated or a gel that can be converted into a sol.
• irreversible colloid : a colloid that once precipitated cannot be dispersed
• emulsion, lyotropic or lyophilic colloid : a stable colloid system in which the dispersed phase is relatively liquid, usually comprising highly complex organic substances, such as starch or glue, which readily absorb solvent, swell, and distribute uniformly through the medium.
• hydrophobic colloid :  a lyophobic colloid in which the solvent is water.
• lyophobic or suspension colloid : an unstable colloid system in which the dispersed phase particles tend to repel liquids, are easily precipitated, and cannot be dispersed with additional solvent.
• hydrophilic colloid : a lyophilic colloid in which the solvent is water.
• protective colloid : a hydrophilic colloid polymer that is able to prevent the precipitation of another colloid by acting as a stabilizer, suspending or thickening agent, or emulsifier.
Marketed products :
• first-generation colloids :
• second-generation colloids :
• human serum albumin (HSA) 20% (Albuminar^®, Albumina Retard^® : yellowish phials) : a preparation of serum albumin fractionated from human whole blood, serum, plasma, or placentas; used as a plasma volume expander for emergency treatment of shock or hemorrhage and to increase the binding capacity for bilirubin in the treatment of hyperbilirubinemia and erythroblastosis fetalis; it has also been used to correct hypoalbuminemia of nephrotic syndrome or cirrhosis. Administered intravenously.
Side effects : neurodevelopmental delays were seen in 5-year-old children treated with human albumin : aluminum, which is introduced into human albumin during processing, may be responsible for the delays since it is a known neurotoxin.
• third-generation colloids : less anaphylaxis and coagulopathy, reduction in the capillary leak (=> less pulmonary oedema and better partial pressure of oxygen in the arterial blood), licensed in Europe for a daily dosage up to 50 mL/kg per day and can be repetitively dosed according to the patient's needs
• starch : 1. any of a group of polysaccharides of the general formula (C₆H₁₀O₅)_n, composed of a long-chain polymer of glucose in the form of amylose and amylopectin; it is the chief storage form of energy reserve (carbohydrates) in plants.  2. a preparation consisting of the granules separated from the mature grain of corn or wheat, or from potato tubers, occurring as irregular, angular, white masses or fine powder; used as a dusting powder and as a filler, binder, and disintegrant in pharmaceutical preparations.
• starch glycerite : a preparation of starch, benzoic acid, purified water, and glycerin; used as an emollient in pharmaceutical preparations intended for external use.
• pregelatinized starch : starch processed to rupture all or part of the granules in the presence of water, and subsequently dried; it occurs as a moderately coarse to fine, white to off-white powder and is used as a tablet excipient in pharmaceutical preparations.
• soluble starch : starch partially hydrolyzed with hydrochloric acid so that it is water soluble; usually amylodextrin.
• 6% hydroxyethyl starch (HES) is the most appropriate artificial colloid (100% volume effect lasting approximately 4 hours with some persisting effect up to 6 hours)
• HES 600 (6% Hetastarch-Baxter^®)
• HES 550 (Hextend^®)
• HES 200 (Elohast^®)
New-generation HES is valuable in trauma patients with head injuries and do not passess the altered BBB. Certain characteristic complications of HES, notably renal impairment, hemorrhage and pruritus, have been well documented with all types of HES solutions. The use of HES solutions with lower molecular weight and substitution has been claimed to minimize these safety risks. In particular, solutions of 200 kDa molecular weight and 0.5 substitution (HES 200/0.5) and of 130 kDa molecular weight and 0.4 substitution (HES 130/0.4) have been advocated for their superior safety profile. A critical appraisal of the available evidence does not provide reassurance that these or other HES solutions are risk free. Most evidence indicates the equivalence of HES 200/0.5 and HES 130/0.4 with respect to effectiveness for volume expansion. Since HES 130/0.4 is newer, its safety profile is less well characterized; however, it appears to share the same complication risks as those of HES 200/0.5. In randomized clinical trials employing sensitive markers, both HES 200/0.5 and HES 130/0.4 have been shown to impair renal function. Both coagulopathy and clinical bleeding have been documented after administration of either HES 200/0.5 or HES 130/0.4, and the magnitude of negative effects on hemostasis has been similar for these two HES solutions. Pruritus is a common side effect of all HES solutions, including HES 200/0.5 and HES 130/0.4, and can occur in diverse clinical settings in some cases after only small HES doses. Typically presenting as pruritic crises of delayed onset, this complication is often severe, protracted and refractory to treatment. An additional risk of HES infusion is the occurrence of potentially life-threatening anaphylactoid reactions, which are 4.5 times as frequent after HES as albumin exposure. Limiting the dose and duration of HES therapy may be helpful in lessening the risk of undesired side effects; at present however, reliance on particular HES solutions does not appear sufficient to ensure safety^ref
• 6% hetastarch (Hespan^®) : a starch containing < 90% of amylopectin, and that has been etherified so that an average of 7 to 8 of the OH groups in every 10-D-glucopyranose units of starch polymer have been converted into OCH₂CH₂OH groups; used as a plasma volume expander, administered by infusion.
• 10% pentastarch : an artificial colloid derived from a waxy starch composed of > 90% amylopectin that has been etherified so that an average of 4 to 5 of the OH groups in every 10 D-glucopyranose units of the starch polymer have been converted to OCH₂CH₂OH groups; used as an adjunct in leukapheresis to increase the erythrocyte sedimentation rate.
• dextran : a high-molecular-weight polymer of D-glucose, produced by enzymes (glycosyltransferases) on the cell surface of certain lactic acid bacteria. Uniform molecular weight dextrans from Leuconostoc mesenteroides preparations are used as plasma volume expanders. Specific preparations are designated, according to their average molecular weight in thousands, as
• dextran 1 (Promit^®) usually prevents anaphylactoid reactions to larger dextrans. When it is administered immediately before dextran 40 or 70, dextran 1 acts as a hapten inhibitor that binds dextran-specific antibodies and blocks larger molecules of dextran 40 or 70 from forming immune complexes. Hapten inhibition with dextran 1 has been found to reduce the incidence of severe dextran-induced anaphylactoid reactions from 1 in 2000 to 1 in 70,000^ref. The Food and Drug Administration's Blood Products Advisory Committee recently recommended adding information about the prophylactic benefit of dextran 1 to the package insert for dextran products to increase awareness among providers^ref. Hapten inhibition reduces the incidence of allergic reaction to dextran solutions. Such reactions are rare in children
• dextran 40
• 6% dextran 70
• and so on
• polygeline : a polymer of urea and polypeptides derived from denatured gelatin; used as a plasma expander in hypovolemia
• 4% succinylated gelatin solution (Eufusin^® (source : Fresenius Kabi Italia S.p.a.); Gelofusine^®; source : Braun NPBI Oss, the Netherlands)
• 3.5% urea-linked gelatin (Emagel^® (+ NaCl + KCl + CaCl₂ + glycerol; source : Aventis Pharma S.p.a.), Gelplex^® (source : Fresenius Kabi Italia S.p.a.); Haemaccel^®; source : Hoechst, Behring-Werke, Marburg Germany) : t_1/2 = 4 hrs; 85% eliminated by renal route; 10% in stools and 2% degraded by proteases
• plasma derivatives are made from pooling up to tens of thousands of units of donated plasma
• source plasma is obtained by plasmapheresis from paid donors.
• recovered plasma is the plasma removed from whole blood donations given by volunteer (unpaid) donors.
Paid donors have higher rates of infection with transfusion-transmissible viruses, but after pooling, the pools are subjected to any of a variety of viral inactivation procedures (for example, pasteurization, nanofiltration, chromatography) that have rendered the risk of infection from these pools negligible since the late 1980s. These derivatives include intravenous immunoglobulin to treat primary immunodeficiencies and some autoimmune syndromes, albumin, and coagulation factor concentrates, used mainly in the treatment of the hemophilias. Derivatives from these huge pools, prior to the mid-1980s before effective screening and viral inactivation, were of course the source of tens of
thousands of HIV-1, HBV, and HCV infections, but viral transmission in the face of viral inactivation procedures applied under the kinds of process control required in most of the developed world is extraordinarily unusual. Process failures leading to contamination of large lots of derivatives,
while rare, remain capable of exposing large numbers of recipients. Transfusable blood components are the labile cells and coagulation factors from whole blood donations. These mainly include red blood cells, platelets, and fresh frozen plasma. They cannot undergo viral inactivation procedures, since that would destroy the therapeutic content of the component. Neither are they pooled in usual practice, so the implications of a virally infected donation extend only to the 2 or 3 recipients of the undetected infected donation. To deal with real and theoretical risks from transfusable components, blood collection facilities in the developed world employ stringent process controls, donor historical screening, reliance on volunteer donors, as well as sensitive and redundant laboratory assays. Viral inactivation techniques that target the nucleic acids of potential pathogens in transfusion components are under development and in various stages of regulatory review around the world, but are not yet in wide use due to a variety of concerns around a number of cost and risk-benefit controversies.
• buffer therapy: i.v. injection of buffer substances with the object of lowering the hydrogen ion concentration
• NaHCO₃
• Shohl solution (1 mmol sodium citrate + 1 mmol citrate/mL)
• osmotherapy : treatment by the intravenous injection of hypertonic solutions to produce dehydration
• thermal medicine in the functional gastrointestinal disorders. The functional dyspepsia, the irritable bowel syndrome, the functional constipation and the functional disorders of the biliary tract (in accordance with Roma II criteria), are the illness for which the drinking mineral waters could give a valid therapeutic support.
• antroteraphy / speleotherapy : treatment of chronic obstructive airways diseases in the conditions of salt mines microclimate in subterranean environments
• peloidotherapy / pelotherapy : the therapeutic use of earth or mud
• hydrotherapy : the application of water in any form, but usually externally, in the treatment of disease. A form of heat treatment for many musculoskeletal disorders. The hydrotherapy tanks and pools are all generally set at warm temperatures, never exceeding 150°F (65.6°C). Because the patient often performs resistance exercises while in the water, higher water temperatures become a concern as the treatment becomes more physically draining. Because of this, many hydrotherapy baths are now being set at 95–110°F (35–43.3°C). There are also units available with moveable turbine jets, which provide a light massage effect. Hydrotherapy is helpful as a warm-up prior to exercise.
• crenotherapy : any treatment incorporating mineral water, mud and vapour
• fluidotherapy : a form of heat treatment developed in the 1970s. It is a dry heat modality consisting of cellulose particles suspended in air. Units come in different sizes and some are restricted to only treating a hand or foot. The turbulence of the gas-solid mixture provides thermal contact with objects that are immersed in the medium. Temperatures of this treatment range from 110–123°F (43.3–50.5°C). Fluidotherapy allows the patient to exercise the limb during the treatment, and also massages the limb, increasing blood flow
• heliotherapy : the treatment of disease by exposing the body to the sun's rays; the therapeutic use of the sun bath
• ampelotherapy : the treatment of disease by grape
• balneotherapy : the treatment of disease by baths
• halotherapy : treatment with the artificially created controlled microclimate
• psammotherapy / ammotherapy / sand therapy : the treatment of disease by sand baths
• climatotherapy / climatotherapeutics : the treatment of disease by means of a favorable climate
• climatothalassotherapy / thalassotherapy : the treatment of disease by sea bathing, sea voyages, and sea air
• aerosolo-therapy : the therapeutic use of aerosols
• aero-iono-therapy : the therapeutic use of e
In contrast to deep heating modalities, superficial heating modalities usually do not heat deep tissues, including muscles, because the subcutaneous layer of fat beneath the skin surface acts as a thermal insulator and inhibits heat transfer. Additionally, increased cutaneous blood flow from superficial heating causes a cooling reaction as it removes the heat that is applied externally. In general, the transfer of heat (whether the purpose is heating or cooling) often is classified into 3 general types of heat transfer (ie, conduction, convection, conversion). Conductive heating is defined as heat transfer from one point to another without noticeable movement in the conducting medium. Typically, direct contact takes place between the heat source and the target tissues. Superficial heat is usually conductive heat (eg, hot water baths, hot packs, electric heating pads, warm compresses). Convective heating is produced by movement of the transferring heating medium, usually either air or fluid. Methods for providing convective superficial heat include fluidotherapy, whirlpool, moist air baths, and hot air baths. The conversion form of heating involves heat transfer by conversion of energy from one energy form (eg, light, sound) to another (heat). Superficial heat is produced by heat lamps or radiant light bakers, where heat is transferred when the conveying medium (light energy) is converted to heat energy at the skin surface. Superficial heat modalities categorized by primary heat transfer mode are summarized as follows:
• conduction - hot packs, paraffin baths
• convection - fluidotherapy, hydrotherapy, moist air
• conversion - radiant heat
Several factors determine the extent of the physiologic response to heat, including the following:
• level of tissue temperature (usually 40-45°C)
• duration of the tissue temperature increase
• rate of increase in tissue temperature
• size of the area being treated
Conductive heating is usually a simple modality that can be taught to the patient for independent home use. The disadvantages of this modality include potential burns, difficulty with application to regions exhibiting abnormalities (eg, foot), and the skin-drying effect (with the exception of paraffin or water media). Another complication that may occur is impairment of local vascular supply, due to a combination of the weight of the modality on the limb or the weight of the limb on the modality. This phenomenon also may be caused by uneven distribution of pressure on the anatomical region that the medium contacts. Hot packs or hydrocollator packs contain silicate gel in a cotton bag. These packs are placed in a hot water tank, which is thermostatically controlled at 71.1-79.4°C. The silicate gel absorbs a large quantity of water and has a high heat capacity. Hot packs are applied over layers of towels for 20-30 minutes. Most of the heat transfer from the hot pack to the patient is by conduction. Increasing the towel thickness reduces the heat flow and produces an intentional slowing in the temperature rise. Acceleration of heat transfer occurs if the hot pack leaks into the towel. The patient never should lie on the hot pack, as the body weight could squeeze hot water out of the pack into the towel and potentially cause a burn. The maximum skin temperature is obtained after 8 minutes, followed by a reduction in temperature due to increased blood flow. Repeated application of hot packs may prolong the period of temperature elevation but does not alter the temperature distribution. Other forms of hot packs include the Kenny pack (vigorous short-term stimulation/heating), rubber hot water bottle, and electric heating pad. Heat transfer is enhanced if the pad is moist or if the heated part is wrapped in moist material. The complications of electric heating pad include shock hazard if the device is not insulated properly and burns if the patient falls asleep lying on the pad. Heat output increases over time until equilibrium is achieved. Keep in mind that heat may be sufficiently analgesic to produce burns. Indications for the application of hot packs may include painful muscle spasms, abdominal muscle cramping, menstrual cramps, and superficial thrombophlebitis. Hospitalized patients receive circulated warm-fluid hot packs to minimize the potential for burns due to prolonged superficial heating application in sensory impaired patients or mentally challenged patients. Chemical packs often are available in containers which, when properly manipulated, allow previously separated ingredients to mix, thereby producing an exothermic chemical reaction that causes heat production. Paraffin bath is another form of conductive heating. Paraffin baths are particularly useful for contractures due to rheumatoid arthritis, burns, and progressive systemic sclerosis (scleroderma). Paraffin usually is applied to the hands, arms, and feet. Paraffin wax is melted and mixed with liquid paraffin. For therapeutic use, the paraffin bath is maintained at the melting point of 51.7-54.4°C in a thermostatically controlled insulated container. The 2 application methods include (1) the dip method and (2) immersion. The hand or foot is placed in the liquid paraffin bath and withdrawn when a thin layer of warm solid paraffin forms, becomes adherent, and covers the skin. The dipping procedure is repeated until a thick paraffin glove is formed. The heat can be retained by wrapping with towels for a period of 20 minutes; then, the cool solid paraffin glove is peeled away and the paraffin is recycled. The dip method is a mild heat application because only a limited amount of heat is available for transfer to the skin.
Immersion :
Alternatively, the body part is immersed in the paraffin bath for 20-30 minutes. The immersion method transfers heat not only from the solid paraffin block but also from the liquid paraffin bath itself. The heat transfer rate from the liquid paraffin bath to the skin is slowed as the solid paraffin glove provides a poor thermal conductor. This modality represents a vigorous heat application, causing a significant increase in skin tissue temperature, up to 46°C, with a marked temperature decrease in the subcutaneous tissue. Water at the same temperature applied by the same method would be intolerable because of the high specific heat and thermal conductivity.
CONVECTIVE HEATING
Fluidotherapy is a form of convective heating that uses a bed of uniform finely divided round solids, such as glass beads, into which thermostatically controlled warm air is blown to generate a semifluid warm mixture. Part of the limb or hand/foot can be immersed for superficial heating. This technique applies dry heat, and the temperature is equivalent to the hot air that is blown into the bed of beads. The usual treatment temperature range is 45.6-47.8°C. Uses of fluidotherapy may include pain relief in arthritic conditions of small joints, joint mobilization following trauma/mobility, and analgesia/sedation in young patients undergoing exercise programs with painful and contracted joints due to sickle cell anemia. Hydrotherapy can include total immersion in a large hot tub or Hubbard tank. Partial immersion is available for upper or lower extremities by whirlpool baths. As hydrotherapy also may be used in treating infected draining wounds, the equipment must be sterilized between uses. The water is agitated, and the size of the tank determines the capacity (the entire body or just the upper or lower extremities). For total body immersion in water, the temperature should not exceed 40.6°C. Partial immersion of a limb should have a maximum temperature of 46.1°C. The treatment time is limited to 20-30 minutes each session. As a precaution for total body immersion, oral temperature should be observed with water temperatures over 37.8°C to prevent a rise of body core temperature. With total body immersion, heat loss occurs primarily through the head and neck; therefore, the heat regulatory mechanism is impaired significantly. Total body immersion has a relaxing effect and may predispose the patient to hypotension due to peripheral blood pooling secondary to vasodilatation of all 4 limbs. Another convection modality is the moist air cabinet. Air saturated with water vapor at a controlled temperature is blown over the patient, causing superficial heating over a large area. The temperature distribution in this modality provides heating of skin and superficial tissue. This modality is used most commonly for back muscle spasms and polyarticular arthritic conditions. The recommended temperature maximum is 40.6°C. Contrast baths provide a method of therapeutic hyperemia for management of rheumatoid arthritis or sympathetically mediated pain (eg, rheumatoid arthritis of distal joints, hands, feet; prolonged ankle swelling after an ankle sprain/strain in refractory joint effusions). A differential of approximately 25°C exists between the hot and cold water. The hot water is at a temperature of 40.6-43.3°C. The cold water temperature is maintained at 15-20°C. The greatest hyperemia response is produced by a 10-minute hot water immersion followed by cold water for 1 minute. The cycle continues with hot water immersion for 4 minutes and cold water for 1 minute; this 4:1 cycle is repeated for a total of 30 minutes at each physical therapy appointment or for each home-based self-treatment session. Other approaches to convective heating include water-based exercise and spa therapy (balneotherapy).
CONVERSION HEATING  Radiant heat therapy is a type of conversion heating. The high-energy photons penetrate the tissues, and this energy is converted to heat. Because photons of longer wavelengths process less energy, penetration is more superficial; shorter wavelengths have a greater therapeutic benefit. The therapeutic radiant heat-producing temperature rise in tissues ranges from the spectrum of far infrared to visible yellow. Longer wavelengths of light from green to ultraviolet produce photochemical reactions that do not raise tissue temperature significantly. Most other commercially available radiant light sources produce infrared with some visible light. These lamps contain heating elements of Carborundum (silicon carbide), special quartz tubes, or metal alloys. The higher energy photons are produced by shorter wavelength radiant heat, resulting in a greater penetration of superficial tissue. The most common indications for radiant heat therapy include muscle spasms from underlying joint/skeletal conditions, rheumatic joints where direct heating of the joint is contraindicated, and treatment of superficial skin breakdown in the intertriginous areas. A treatment time of 20-30 minutes is recommended, with the maximum effect occurring at a minimum of 20 minutes. The radiant energy source is positioned at 15-24 inches (38.1-61 cm) from the treatment site. The intensity is controlled by the light source, distance, type/quality of reflector, and air movement. With heat lamps, guidance concerning treatment time is given by the patient's subjective feeling of warmth. The conventional single heat cradle with an output of 300 watts is not likely to increase body temperature; however, a double cradle could. Patients also could receive increased radiation after an hour of treatment time. Infrared radiation can be used for reflex vasodilatation where vasospasm is present. Because of the photochemical effect of lower energy ultraviolet photons, this radiant energy is used most effectively for treatment of psoriasis and other dermatologic conditions.  CONTRAINDICATIONS TO SUPERFICIAL HEAT APPLICATION
Superficial heat modalities are contraindicated in the following situations:
• Paraffin baths or fluidotherapy should not be used in open wounds that are either clean or infected.
• Hydrotherapy is contraindicated in patients immediately following surgery, as a healing wound should be kept dry.
• Special precautions should be used for therapy to be provided in a Hubbard tank for patients with either a tracheostomy or ostomy.
• radiant heat should not be used in patients with the following conditions:
• Photosensitivity
• Acute inflammation or hemorrhage
• Bleeding disorder
• Decreased sensation
Because total immersion in a Hubbard tank elevates core body temperature, patients with the following conditions that generate temperature-sensitivity should avoid this heating modality:
• Multiple sclerosis
• Adrenal suppression or failure
• systemic lupus erythematosus
• Pregnancy
THERAPEUTIC COLD (CRYOTHERAPY)
Cryotherapy has the primary effect of cooling tissue. Depending upon the application method and duration, the basic physiologic effects include the following:
• Decreased local metabolism
• Vasoconstriction
• Reactive hyperemia
• Reduced swelling/edema
• Decreased hemorrhage
• Reduced muscle efficiency
• Analgesia secondary to impaired neuromuscular transmission
Pain reduction associated with application of cold relaxes muscle spasm and minimizes upper motor neuron spasticity. The most common indications and uses for local application of therapeutic cold modalities include the following:
• To decrease swelling/edema following trauma (cooling in water at 8°C for 30 minutes decreases edema)
• To treat burns
• To inhibit spasticity (in spasticity, the muscle must be cooled; this process takes 10 minutes in thin patients and up to 60 minutes in more obese persons)
• To reduce muscle spasm
• To reduce acute inflammatory reaction
• To reduce pain
• To reduce limb metabolism (prior to amputation)
• To produce reactive hyperemia
• To facilitate muscular contraction for various forms of neurogenic weakness and for muscle re-education
• Immediate application of ice or cold packs for superficial burns and burns of less than 20% total body surface area decreases pain, edema, erythema, and blistering. For optimal results in cases of trauma, cold should be applied before significant edema and hemorrhage occur.
The most common methods of cold application include cold packs, cold immersion, ice massage, and cooling during exercise (cryokinetics). Spray and stretch is an application of cryotherapy with a vapocoolant spray, which then is followed by stretching of the involved muscles. This technique sometimes is used in the management of myofascial pain syndromes, as described by Travell and Simons. Therapeutic cold is applied for 5-20 minutes, followed by a rest period of 30 minutes. For treatment of acute sprains/strains and postoperative care, application of cold is recommended for the first 24-48 hours. For treatment of deeper tissues or for prolonged periods of cold application, physician evaluation/prescription is essential to avoid complications. The most useful local therapeutic cold applications include management of edema, muscle spasm, bleeding, and traumatic pain. The vasoconstriction effect of therapeutic cold is beneficial for reducing posttraumatic swelling and pain or for reducing hemorrhage into soft tissues. The following are conditions for which local cryotherapy is contraindicated:
• Hypertension (due to secondary vasoconstriction)
• Raynaud disease
• rheumatoid arthritis
• Local limb ischemia
• History of vascular impairment, such as frostbite or arteriosclerosis
• Cold allergy (cold urticaria)
• Paroxysmal cold hemoglobinuria
• Cryoglobulinemia or any disease that produces a marked cold pressor response
Cold packs applied to the abdomen cause increased gastrointestinal motility and gastric acid secretion; therefore, this treatment is contraindicated in those with known peptic ulcer disease. Interestingly, application of hot packs to the abdomen produces the opposite effect.
COLD VERSUS HEAT THERAPY
Both heat and cold modalities can be used effectively in various clinical conditions. Many situations lend themselves to use of these diverse modalities to take advantage of known biologic effects for managing certain ailments. The similarities of these 2 modalities include the following:
• Decreased muscle spasm secondary to musculoskeletal pathology or nerve root irritation
• Cold effectively decreases spasticity of upper motor neuron etiology; heat reduces spasticity, but the effects are short-lived and ineffective for muscle re-education.
• Both heat and cold modalities cause analgesia.
The following examples illustrate the significant differences in the physiological effects between therapeutic heat and cold treatments:
• A longer time is necessary for cooled muscle to return to normal temperature. Because application of heat increases blood flow, a heated muscle returns to normal temperature after a few minutes.
• The application of heat for relief of muscle spasm is secondary to muscle hyperemia, which decreases muscle spasm-induced ischemia/pain and interrupts this vicious cycle.
• Increased tissue metabolism occurs with temperature elevation; reduced metabolism with cold modalities.
• Heated muscle tissue can sustain a contraction for a shorter period of time; cooling to approximately 27°C increases the ability of muscle to sustain contraction.
• Blood flow increases with heat and decreases with cold.
• The tendency to bleed increases with heat and decreases with cold.
• Formation of edema is facilitated by heat and decreased by cooling.
• Immediate cooling of burns is beneficial; however, frostbite is treated by quick warming.
• Joint stiffness is decreased with heating but increased with cold.
Due to blood pooling, orthostatic hypotension is produced by application of heat to large parts or all of the body. With cold treatment, hypotension is decreased secondary to vasoconstriction^{ref1, ref2, ref3, ref4}
• trace elements
• iron (Fe)
• oral supplementation :
• ferrous sulfate / iron sulfate / FeSO₄^. 7H₂O (Feosol^®, Feospan^®, Feratab^®, Fer-gen-sol^®, Fer-in-sol^®, Fer-Iron^®, Ferodan Syrup^®, Fero-Gradumet^®, Ferospace^®, Ferralyn^®, Ferra-TD^®, Ferrograd^®, Ferrogradumet^®, Ferromin^®, Fertonic^®, ...; Feral-Z^® in combination with folic acid and zinc sulphate; Ferrograd-folic^® in combination with folic acid)
• ferrous fumarate (Feostat^®, Ferretts^®, Ferumat^®, ...)
• ferrous gluconate (Fergon^®, Ferralet^®, Fertinic^®, ...)
• iron bis(glycinate) chelate (Ferrochel^®, )
• polysaccharide-iron complex (Niferex^®, ...)
• iron citrate (Fer-Sol^®)
• liposomal iron pyrophosphate (Lipofer^®; SiderAL^® in combination with vitamin C and vitamin B₁₂)
• edetate
Side effects : constipation (50%) or diarrhea (50%)
• parenteral supplementation :
• iron dextran (Infed^®, Dexferrum^®)
• iron saccharate (Ferosac IV^®)
• ferric hydroxide polymaltose (Ferose^®)
• sodium ferric gluconate complex in sucrose (Ferrlecit^®, Ferlixit^®)
• copper (Cu)
• zinc : zinc supplementation is beneficial in the management of a number of conditions, including acute diarrhea, the common cold, acne and progressive myoclonic epilepsy. Its putative effect is the enhancement of immune function. Many over-the-counter (OTC) zinc-lozenge products are now available; in 1989, an estimated 16% of US citizens were taking zinc supplements orally.
• calcium (Ca²⁺) (Cacit^®)
• monofluorophosphate calcium salts (Tridin^®, Trinidal-F^®)
• sodium monofluorophosphate (Monotridin^®)
• calcium carbonate (Vitatridin^®, Calcitridin^®, Metocal^®)
• chromium (Cr³⁺) : supplement is absorbed better than dietary chromium. Chromium supplementation in people with chromium deficiency can improve glucose tolerance and some lipid metabolism parameters, lower cholesterol, and aid muscle development. The supplementation is indicated in persons with impaired glucose tolerance both in preclinical and manifested stadium of type 2 diabetes mellitus where increased lost of chromium in urine was documented. In these patients, chromium deficiency can participate in insulin resistance and hyperlipidaemia. Chromium is usually applied in the form of
• organic compounds
• yeast extract
• chromium picolinate (Natural Performance Chromium Picolinate^®, CVS Chromium Picolinate^®, Chromium picolinate^®, Pyruvate C Weight Loss Program^®, Fat Burners^®, Chroma Slim for men^®, Diet System 6^®, Ultra Chroma Slim^®, Ultraburn Chromium^®, Ultraformula Fat Burner^®, Chroma-trim gum^®). Cr(III) picolinate is purchased almost as often from supermarket shelves as are calcium supplements, yielding hundreds of millions of dollars yearly in sales. However, the unregulated sales of this supplement are now attracting criticism because there are indications of little efficacy in glucose homeostasis and of significant carcinogenicity (see chromium toxicity)


• glucose tolerance factor : a biologically active complex of chromium and nicotinic acid that facilitates the reaction of insulin with receptor sites on tissues (see chromium toxicity)
• chromium chloride
• iodine (I^-)

Indications :
• accidental contamination from radioactive isotopes
• thyrotoxic crisis (Wolff-Chaikoff effect)
• before thyroid surgery
• endemic goitre
• magnesium (Mg²⁺)
• selenium (Se)
• sodium fluoride / disodium difluoride : Floridine^®; Florocid^®; Villiaumite^®; NaF^®; Sodium hydrofluoride^®; Sodium monofluoride^®; Trisodium trifluoride^®; Alcoa sodium fluoride^®; Antibulit^®; Cavi-trol^®; Chemifluor^®; Credo^®; Duraphat^®; Fda 0101^®; F1-tabs^®; Flozenges^®; Fluoral^®; Fluorident^®; Fluorigard^®; Fluorineed^®; Fluorinse^®; Fluoritab^®; Fluorocid^®; Fluor-o-kote^®; Fluorol^®; Fluoros^®; Flura^®; Flura-gel^®; Flura-loz^®; Flurcare^®; Flursol^®; Fungol b^®; Gel II^®; Gelution^®; Gleem^®; Iradicav^®; Karidium^®; Karigel^®; Kari-rinse^®; Lea-cov^®; Lemoflur^®; Luride^®; Luride lozi-tabs^®; Luride-sf^®; Nafeen^®; Nafpak^®; Na frinse^®; Nufluor^®; Ossalin^®; Ossin^®; Osteofluor^®; Pediaflor^®; Pedident^®; Pennwhite^®; Pergantene^®; Phos-flur^®; Point two^®; Predent^®; Rafluor^®; Rescue squad^®; Roach salt^®; Sodium fluoride cyclic dimer^®; So-flo^®; Stay-flo^®; Studafluor^®; Super-dent^®; T-fluoride^®; Thera-flur^®; Thera-flur-n^®; Zymafluor^®; Les-cav^®; Sodium Fluoride^®
• amino acids : Corynebacterium efficiens is used for the industrial production of amino acids. Researchers are interested in this organism primarily owing to its ability to grow and produce amino acids at 40°C — 10°C higher than the closely related and commonly used industrial strain, Corynebacterium glutamicum. This feature offers potential savings in cooling costs for large-scale fermentation. Nishio et al. have compared the complete genomes of these two bacteria to reveal the three most common amino acid substitutions that they conclude to be most likely to contribute to the increased protein thermostability in C. efficiens. Detailed analysis showed that although the increase in G+C content of the genome (63% compared with 54% for C. glutamicum) correlates with a shift in codon usage, it cannot account for all the thermostabilising amino acid changes.
• FreAmine II^® : trademark for a crystalline amino acid solution for intravenous administration, containing a mixture of essential and nonessential amino acids but no peptides.
• L-ornithine
• S-adenosyl-L-methionine (Samyr^®)
• advanced nutritional supplements / nutraceuticals / functional foods : foods and food supplements marketed for presumed health benefits, such as
• vitamin supplements
• certain herbs or other botanicals
• melatonin
• chromium picolinate : used by some to control blood sugar levels or to lose weight  ; appears to be generally safe
• chaparral : also known as greasewood or creosote bush, is thought to fight intestinal parasites and treat colds, flu and diarrhea ; may cause adverse effects in some particular users
• glucosamine sulfate (Adaxil^®, Arthroaid^®, Arthryl^®, Bioflex^®, Bipron^®, Dona^®, Osteomin^®, Praxis^®, Viartril-S^®, Xicil^®) : used by some to treat joint pain and osteoarthritis (OA) (2 3-year studies indicate that it may reduce symptoms and stabilise radiographic minimal joint space width compared to placebo in postmenopausal women with knee OA); may cause adverse effects in some particular users
• hyaluronic acid (Go-On^®) : viscosupplementation for synovial fluid
• saw palmetto : a small creeping palm of the southeastern USA, Serenoa repens. The fatty-acid fraction of saw palmetto may be the active ingredient of the berry extract and that most products contain 85 to 95 percent fatty acids. The partially dried, ripe fruit of the saw palmetto, is used by over 2 million men in the USA for urination problems associated with benign prostatic hypertrophy (BPH) and hair loss; may cause adverse effects in some particular users. Sales of saw palmetto are growing, with an estimated $131 million of the product consumed by Americans in 2000. A RCT showed that 160 mg of saw palmetto taken twice daily did not improve symptoms or objective measures of benign prostatic hyperplasia^ref. Since saw palmetto is available in higher doses than 160 mg, would it not be expected that the higher-dose capsules contain more of the supposed active ingredient and thus would be more effective than the 160-mg dose? A recent systematic review of 21 randomized, controlled trials of saw palmetto found that 15 studies used a dose of 160 mg twice a day, and 5 studies used lower doses; only 1 study used a higher dose^ref
• African plum (Pygeum africanum): likely effective for the symptomatic treatment of benign prostatic hypertrophy (BPH)
• shark cartilage : thought by some to be effective against cancer
• 5-Loxin is a standardized extract of boswellic acid. The patented extraction process means it delivers 30% 3-acetyl-11-keto-b boswellic acid (AKBA), the most potent boswellic acid extract, compared with just 2-3% by other extracts. It has been available to dietary supplements formulators through PL Thomas since December 2004, was the first formal offering to come out of the ingredients supplier’s recently announced alliance with Laila Nutraceuticals^ref
In the USA, > 60% of doctors have referred patients for services that are complementary to conventional western medicine (CWM). Around 29,000 dietary supplements are available in US drugstores, and Americans spend around US$16 billion on them each year. Fears over their potential risks escalated last year after the death of baseball player Steve Bechler, who was taking the weight-loss and energy aid ephedra. While it was unclear if his death was caused by the supplement, the FDA subsequently introduced a ban on ephedra, effective from 12 April 2004. The National Academies' Institute of Medicine recommends that manufacturers should be obliged to report adverse events attributable to dietary supplements to the FDA. It has been estimated that < 0.5% of such events are currently reported
• artificial alimentation (see also diet) : the giving of food or nourishment to persons who cannot take it in the usual way, to prevent malnutrition
• gavage : forced feeding, especially through a tube passed into the stomach.  2. the therapeutic use of a very full diet; superalimentation
History :
• 1900 : i.v. glucose solutions
• 1937 : crescin hydrolysis
• 1940 : amino acids
• 1961 : lipids
• 1968 : hypertonic glucose solutions
Energy metabolism.
Calorie requirements for an average (70 kg) adult man :
• basal and minor surgery : 1450 kcal/day
• mild peritonitis : + 25%
• postoperative (uncomplicated : 1500-1700 kcal/day
• sepsis : 2,000-2,400 kcal/day
• multiple trauma (ventilator) : 2,200-2,600 kcal/day
• burns : 2,500-3,000 kcal/day
A tissue trauma in a polytraumatized patient is different from a circumscribed surgical ablation : in the first case hypotension leads to vasoconstriction and ischemic necrosis, there is no sterility and the patient experiences pain, anguish and anxiety which activate sympathetic responses. In the second case there are controlled tissue losses (e.g. vessel ligation), there is sterility and pain is controlled during and eventually even after surgery.
Routes of administrations (ROA) :
• enteral nutrition : the delivery of nutrients in liquid form directly into the stomach, duodenum or jejunum; used when the patient's condition precludes oral intake; first used for predigested proteins for dogs

Requirements : normal appetite and gastrointestinal functions
Advantages :
• maintain villous trophism
• safe, simple and anatomical delivery
Contraindications :
• absolute :
• untreatable vomiting
• intestinal occlusion
• gastrointestinal bleeding
• relative :
• diarrhea
• ascitis
• intra-abdominal infections
• nasogastric tube

Indications :
• anorexia nervosa
• depression
• esophageal or pyloric obstruction
• weight loss 20-30%
• chronic dysphagia
• starvation longer than 3-4 days after surgery
Placement :
• use the better opened narix
• lubrifying and anaesthetic agents
• seated patients with flexed head
• narix-ear measurement to calculate when the probe reaches the nasopharynx. When the probe is placed there, the patient is asked to drink and the probe is swallowed down together with water.
• check with phonendoscope the inflation of stomach during inspiration (absent if the probe has been placed in trachea)
• place the patient on the right flank and await a few hours for gastric peristalsis to move the probe across pylorus
Small silicon catheters allow lower esophageal sphincter (LES) closure and prevent GERD and rhinopharyngeal irritation. In urgencies : central venous catheters (CVC) or alimentary jejunostomy.
Solutions :
• polymeric solutions (obtained with homogenizers => require large probes)
• chemically defined solutions
• modular solutions (chemically defined formula for patient with impaired digestive function) : monomers/short chain molecules, + MCI, + essential fatty acids (EFA), lactose-free. One or more macronutrients (proteins, carbohydrates, lipids) according to their solubility, interactions and osmolarity
• daily diet, via gastrojejunal feeding tube : 1000 mL of Jevity (Abbott Laboratories Ltd., Montreal, Que.) and 375 mL of Nutren 1.5 (Nestlé Clinical Nutrition Company, Deerfield, Ill.).
Risks : malpositioning of catheter in trachea or esophagus (aspiration) => for safety reasons it is usually placed over the pyloric sphincter. Lift the body during and after administration of the nutrition. Check up gastric emptying.
Side effects :
• meteorism
• distention
• nausea
• diarrhea

Aetiology :
• excessive volume
• hyperosmolar solution
• atrophic malabsorption
Prevention :
• decreased infusion rate
• decrease osmolarity
• opium tincture

Side effect : distention and constipation in elderlies
• dumping syndrome if lower than pylorus
• metabolic side effects are rarer than with parenteral nutrition : hyperosmolarity, diarrhea, hyperglycemia (pancreas isn't activate by pyloric delivery)
• rectal alimentation : the administration of concentrated nourishment by instillation into the rectum
• parenteral alimentation : administration of nutriment intravenously
• total parenteral nutrition (TPN), alimentation or hyperalimentation : the intravenous administration of the total nutrient requirements of the patient with gastrointestinal dysfunction
History : introduced in Europe in 1960 (lipids) and in USA (hypertonic glucose solutions) in 1965
Routes of administration :
• central venous catheters (CVC) (usually inserted in the superior vena cava via internal jugular or subclavian vein) for hyperosmolar solutions

Side effects : phlebitis
• peripheral vein
Requirements :
• sterile conditions
• solutions :
• L-amino acids (4 kcal/g)
• branched
• essential (Ala, His, Pro, Arg)
• Glc 5-35% (5-10% for peripheral accesses) (3.4 kcal/g => G/A 5% => 170 kcal/L; G/A 25% => 850 kcal/L); when infused at excessive rate it may cause hyperosmolarity
• electrolytes
• vitamins
• lipid emulsion (9 kca/g : 15-40% of total calories) 10-20% + glycerol 2.5% (isotonic). Some people do not tolerate milky blood. Administer no more than 4 g/kg/day and 500 mL of 10% solution per week to administer essential fatty acids and 15-30% of calorie requirements- Higher doses could lead to acute respiratory failure
• Lipofundin^® : soy seed oil + lecithin + glycerol
• Clinimix^® :
Regimen of delivery :
• home parenteral nutrition (HPN)
Indications : total malfunctioning of gastrointestinal tract
Complications :
• mechanical (1-3%) :
• catheter tip misplacement (CXR) : tip of catheter directed outside of superior vena cava or right atrium

Treatment : redirect with a guide wire under fluoroscopy
Prevention : direct bevel of needle caudally
• pneumothorax from puncture or laceration of lung pleura (dyspnea, CXR)

Treatment : tube thoracostomy if indicated, observation
Prevention : avoid emergency procedures, Trendelenburg's position
• hemothorax (dyspnea, CXR)

Treatment : remove catheter, observation
Prevention : insert catheter using appropriate techniques
• subclavian vein thrombosis secondary to catheter (inability to cannulate)

Treatment : remove catheter, heparin therapy if clinical significant
Prevention : use silicone catheters, add heparin to solution
subclavian vein perforation
• subclavian artery perforation during needlestick (pulsatile red blood)

Treatment : remove needle, apply pressure, CXR, serial monitoring of vital signs
Prevention : review anatomy
• embolism
• air embolism due to aspiration of air into the subclavian vein and right side of the heart (coming in during breathing when the external opening of the catheter is deconnected) (dyspnea, cyanosis, hypotension, tachycardia, precordial murmur)

Treatment : Trendelenburg's position, left lateral decubitus position, aspirate air
Prevention : Trendelenburg's position, Valsalva maneuver, tape intravenous connection
• catheter embolism (sheared catheter)

Treatment : fluoroscopic retrieval transvenously
Prevention : never withdraw catheter through needle
• arrhythmias (catheter tip in right atrium)

Treatment : withdrawn catheter to superior vena cava
Prevention : estimate distance to SVC before insertion, confirm position with CXR
• cardiac tamponade
• central venous thrombosis
• infectious complications :
• Staphylococcus aureus
• Candida albicans
• line sepsis (catheter tip infected)

Treatment : remove catheter, antibiotics
• infection at skinsite (bacteria at site of catheter entry into skin)

Treatment : remove catheter, local wound care
• metabolic complications :
• acute CHF
• increased [insulin, T₄, cortisol]_plasma due to excessive glucose calories or glucose intolerance. If the at the beginning hyperglycemia and hyperosmolar nonketotic coma (due to dehydration with excessive osmotic diuresis : disorientation, lethargy, stupor, convulsions, coma, glucose 1,000 mg/dL, osmolarity 350 mOsm/kg) appear interrupt administration and inject 2 L of 20% glucose solution => if the patient experiences hypoglycemia, decrease glucose content to 5% for 12-24 hours.

Treatment : discontinue TPN immediately: infuse D5 in 0.45% S at 250 mL/hr, insulin 10-20 U/hr, bicarbonate, monitor glucose and electrolytes, potassium, pH
Prevention : monitor glucose
• hypoglycemia due to sudden cessation of TPN (headache, sweating, thirst, convulsions, disorientation, paresthesias)

Treatment : bolus D50W I.V.; monitor blood glucose
Prevention : taper TPN by 1/2 for 12 hr; then 12 hr of D5W at 100 mL/hr
• CO₂ retention (hypercarbia) due to infusion of glucose calories in excess of energy needs (ventilator dependance, high respiratory quotient)

Treatment : decrease glucose calories and replace with fa
Prevention : provide 30-40% of calories with fat
• hyperchloremic metabolic acidosis due to excessive chloride administration

Therapy : give sodium and potassium as acetate salts
• azotemia due to excessive amino acid administration with inadequate calories (dehydration, elevated BUN)

Treatment : decrease amino acids and increase nonprotein (glucose) calories
Prevention : monitor fluid balance
• hyperammonemia (lethargy, malaise, coma, seizures)

Treatment : discontinue amino acid infusions, infuse arginine
Prevention : avoid casein or fibrin hydrolysate
• essential fatty acid deficiency due to inadequate administration (xerosis, hepatomegaly, impaired hearing, bone changes)

Treatment : administer fat solution
Prevention : provide 25-200 mg/kg/day of essential fatty acids
• hypertriglyceridemia due to rapid fat infusion of decreased fat clearance

Therapy : slow rate of fat infusion
• hypophosphatemia due to inadequate administration (lethargy, anorexia, weakness)

Treatment : supplemental phosphate
Prevention : treat causative factors: alkalosis, gram-negative sepsis, vomiting, malabsorption. Provide 20 mEq/kcal
• abnormal liver enzyme (fatty infiltrate in liver)

Treatment : evaluate for other causes
Prevention : provide balanced TPN solution
• hypomagnesemia (weakness, nausea, vomiting, tremors, depression, hyporeflexia)

Treatment : infuse 10% MgSO₄
Prevention : supply 0.35-0.45 mEq/kg/day
• hypermagnesemia (drowsiness, nausea, vomiting, coma, arrhythmias)

Treatment : dialysis, infuse calcium gluconate
Prevention : monitor serum levels
• increased metabolic expenditure
• increased O₂ consume
• increased cardiac output
• bleeding due to vitamin K deficiency

Treatment : administer vitamin K
Side effects :
• cholestasis
• if the nitrogen balance remains negative despite adequate protein intake, add glucose to the daily dose
• biopharmaceuticals (proteins (except antibodies) and nucleic acids (except gene therapy)
Their immunogenicity depends on :
• structural properties
• sequence variation due to foreign origin
• non-glycosylation pattern due to production in bacterial vectors : it may lead to
• exposure of antigenic sites
• reduced solubility
• lack of tolerance if the deficiency is innate
• contaminants and impurities from initial production or downstream processing
• protein modifications
• oxidation
• deamidation
• aggregate formation (reduced by addition of human serum albumin (HSA) and/or PEGylation)
• route of administration (intramuscular and subcutaneous routes are more immunogenic than intravenous or local treatment)
• dose
• length of treatment
• immunocompetence of the patient
• unknown factors
The consequences of antibody production may be :
• none
• loss of efficacy of the biopharmaceuticals (it can possibly be overcome by increasing the dose) (eg for rhuEPO^ref)
• enhancement of efficacy of the biopharmaceuticals
• neutralization of the native endogenous factor, too. When the endogenous factor mediates a unique biological function, a clinical syndrome develops. Such has been observed in immune responses to recombinant erythropoietin and thrombopoietin, with patients exhibiting pure red blood cell aplasia and immune mediated thrombocytopaenia respectively.
Immunogenicity may be predicted by :
• degree of distribution of homology
• physicochemical characterization for biopharmaceuticals that have a high degree of homology
• animal models
• non-human primates
• transgenic animals (so immune tolerant for the human protein that they express)
• nonprotein autacoid replacement therapy
• PGE₁ : alprostadil (Prostin VR Pediatric^®)
• topical cream : Alista™, Femprox^®
• gel : Topiglan^®
• urethral suppository : medicated urethral system for erection (MUSE^®)
• intracavernosal injection (Caverject^®, Edex^®)
• PGE₂ : dinoprostone (Carverject^®, Prepidil^®)
• PGI₂ / prostacyclin (PC) : epoprostenol (Flolan^®), treprostinil (Remodulin^®), beraprost (Dorner^®, Procylin^®), and iloprost (Ilomedin^®)
• adenosine (Ado) (Adenocard^®)
• nitric oxide (NO) (INOvent^®)^ref

Clinical indications for administering inhaled nitric oxide to adults :
• acute lung injury and the ARDS
• targeting pulmonary vascular resistance
• lung transplantation
• sickle cell disease
Alternatives and adjuncts to inhaled nitric oxide :
• other inhaled vasodilators
• adjunctive therapies that increase the effectiveness of inhaled nitric oxide
• nonprotein neurotransmitters replacement therapy
• acetylcholine (Miochol-E^®)
• dopamine hydrochloride (Dobutrex^®, Intropin^®, Revivan^®)
• epinephrine / adrenalin (Epinal^®, Epifrin^®, Fastjekt^®, Fastjeckt Junior^®, Glaucon^®)
• norepinephrine / noradrenalin : levarterenol (Levophed^®)
• histamine dihydrochloride (Ceplene^®; source : Maxim Pharmaceuticals) : prevents monocytes, macrophages and neutrophils typically present in large quantities in diseased, cancerous and virally infected tissues, from releasing ROS that have been shown to induce apoptosis in NK, NKT and T cells (see immunooncology). In clinical trials for malignant melanoma (together with IL-2^{ref1, ref2, ref3, ref4, ref5}), renal cell carcinoma, and hepatitis C (together with IFN-a_2b)^ref
• melatonin : used by some to treat insomnia, depression, and jet lag syndrome ; appears to be generally safe
• protein replacement therapy (click here for transfection techniques) : nearly $10 billion worth of biopharmaceuticals are expected to come off patent during the next 5 years, and firms that produce generic drugs want to jump in to exploit the niche. The lure of less expensive medication is strong: The biogenerics market is expected to reach $16 billion by 2007. Biopharmaceutical medications are among the most expensive of drugs; some cancer treatments can cost $10,000 a month. Generics (biogenerics), on the other hand, can sell for as little as one-fifth the price of the original drug. Many generic biologic drugs are already sold in unregulated markets in China, Eastern Europe, India, Brazil, Peru, Egypt, and Mexico. Sicor Pharmaceuticals of Irvine, Calif., has made a generic version of interferon alpha-2b for more than a decade and is selling it in 17 countries. Vancouver-based Dragon Pharmaceuticals sells a version of Amgen's Epogen, a genetically engineered copy of erythropoietin (EPO), in 5 countries. Dragon is already eyeing the European Union for its generic version of EPO, with hopes of selling it there as early as 2006. The patent for synthetic human hormone EPO is set to expire there this month. Marketed as Epogen by Amgen and Procrit by Johnson & Johnson, the drug had combined US sales of more than $6 billion in 2003. But the Sandoz case demonstrates that European regulators still remain at cross-purposes as to how to interpret new rules for making and selling biogenerics. European regulators required Sandoz to conduct two sets of clinical trials on Omnitrope. Though the European Medicines Evaluation Agency (EMEA), the region's equivalent of the FDA, recommended approval of Omnitrope in June 2003, the European Commission denied approval this past March while it considers whether the Sandoz clinical trials were sufficient. The disagreement between the two agencies is considered unusual, and it demonstrates what many believe are continuing interpretive differences over rules that are just now being tested. The fact that Sandoz filed for Omnitrope approval before the European guidelines came out last December indicates that future applications may have an easier time. Moreover, Australia's approval of Omnitrope will provide Europe with some regulatory precedent.



• cytokines replacement therapy
• interferons (IFNs). The lowercase letter is assigned by the drug nomenclature agencies to differentiate one manufacturer's interferon from another's. For mixtures of naturally occurring interferons obtained from a natural source, whether the exact percentage of a mixture is known or not, the lower case letter "n" precedes the number
• IFN-a / leukocyte interferon is currently in phase III clinical trials to enhance tumour antigen presentation and cytotoxicity (systemic route)^ref. Indications : chronic myeloid leukemia (CML)
• rIFN-a_con-1
• Infergen^®; source : InterMune, Inc., SOL(0.03 mg / mL)SC
• IFN-a₂ :
• rIFN-a₂ :
• Roferon A^®; cloned in Escherichia coli; source : F.Hoffmann-La Roche/Genentech. Prefilled syringe sc in 3, 6, and 9 MIU concentrations for self-administered therapy of CML. Most frequently reported adverse reactions at > 10% (9MIU/day) : fever, asthenia or fatigue, myalgia, chills, anorexia, arthralgia/bone pain, headache, nausea/vomiting, diarrhea, depression, coughing, hair changes (including alopecia), skin rash, decreased mental status, sweating, dizziness, and sleep disturbances. Depression, together with suicidal ideation, suicide attempts, and suicides have been reported in association with alfa interferon therapy. Roferon-A should be used with caution in patients with severe preexisting cardiac disease, severe renal or hepatic disease, seizure disorders, and/or compromised CNS function
• Canferon A^®
• PEGylatedrIFN-a₂ :
• Pegasys^® (source : Roche). Indications : HBeAg⁺ and HBeAg^- chronic hepatitis B.
Indications : HBV and HCV infections, renal cell carcinoma and multiple myeloma
Neutralizing antibodies may emerge during retreatment but do not affect endogenous IFN-b or IFN-a_C^ref : they can be measured with a replicon-based bioassay^ref
• rIFN-a_2b :
• Intron A^®; cloned in Escherichia coli; source : Schering-Plough, Ireland and Biogen, LIQ(15,000,000 U / mL, 25,000,000 U / mL, 50,000,000 U / mL)SC
• PEGylated rIFN-a_2b :
• Peg-Intron^®; source : Schering-Plough, PWSO(74 mg / vial, 118.4 mg / vial, 177.6 mg / vial, 222 mg / vial)SC. Also administered via a pre-filled pen (Peg-Intron Redipen^®)
Following an i.v. dose of 30 million IU, the amount of rIFN-a_2b transferred into human milk was only slightly elevated (1551 IU/mL) when compared to control milk (1249 IU/mL). These data suggest that even following enormous doses, interferon is probably too large in molecular weight to transfer into human milk in clinically relevant amounts^ref.
Premedication : acetaminophen 650 mg PO 30 minutes prior to treatment, repeat q4h PRN
Indications : chronic myeloproliferative syndromes
• rIFN-a_n1 :
• Wellferon^®
• rIFN-a_n2
• rIFN-a_n3 :
• Alferon N^®
Regimen : 3 MIU SQ 3 times/wk
Complications : autoimmune disorders, including thyroiditis and vitiligo, have been reported to develop in 15-30% of patients who receive IFN-a therapy. Yet an association between the development of autoimmunity and responsiveness to immunotherapy has largely been restricted to melanoma and renal cell cancer
• IFN-b₁ / fibroblast interferon :
• rIFN-b_1a :
• Avonex^®; cloned in CHO cells; source : Biogen, Inc, USA. Alternate supplier for HSA as excipient, PWSO(30mcg/kit)IM
• Rebif^®; cloned in chinese hamster cells; source : Interpharm Laboratories Ltd => Serono Canada Inc., LIQ (22 mg / syr, 44 mg / syr) IL, SC, PWSO (11 mg / vial, 44 mg / vial) IL, SC
• rIFN-b_1b :
• Betaferon^® : cloned in Escherichia coli or CHO cells; source : Chiron Corp, USA
• Betaseron^®; source : Berlex Canada Inc. Alternate supplier for HSA used as excipient in manufacture of Betaseron, PWSO(0.3mg/vial)SC)
Regimen : 6 MIU SQ 3 times/wk
• IFN-g₁ :
• rIFN-g_1a (Immuneron^®) (source : Biogen and Baxter) prepared from Escherichia coli
• rIFN-g_1b :
• Actimmune^® expressed in Escherichia coli; source : Genentech, Inc. Noncovalent dimer. Low resolution crystal structure available. Monomer consists of 140 amino acids (QDPYVKEAENLKKYFNAGHSDVADNGTLFLGILKNWKEESDRKIMQSQIVSFYFKLFKNFKDDQSI

QKSVETIKEDMNVKFFNSNKKKRDDFEKLTNYSVTDLNVQRKAIHELIQVMAELSPAAKTGKRKRS
QMLFRGRRASQ), no glycosylation or cysteines in human form. Murine form is a covalent dimer (one cysteine per monomer). Monomer 16.44 kD^ref. Standard human dose is 100 µg. High doses can cause significant side effects such as nausea, fever, and other flu-like symptoms. Effect of molecule is specific to species. Human form does not elicit toxicity in lower species at several mg/kg doses which are toxic to humans. Higher and earlier neutralizing antibody titers, increase in duration of neutralizing antibody titers, increase in MHC class II expression on APCs, increase in T_h cell levels, and an improved DTH response have all been observed when IFN-garnma was administered with an antigen. The IFN-g must be given at the same site and at the same time (within 6 hrs) as the antigen to have biological
effect^{ref1, ref2} [Heath, A. W. and Playfair, J. H. L., 1992, Cytokines as immunological adjuvants, Vaccine, 10:427-434; Heath, A., 1995, Cytokines as immunological adjuvants, in: Vaccine Design M. F. Powell and M. J Newman (Eds.) Pharmaceutical Biotechnology Series, Plenum Publishing Corp., New York; Dong, P., 1995, Cytokines as immunological adjuvants: Current status and potential applications, in: Vaccine Design M. F. Powell and M. J Newman (Eds.) Pharmaceutical Biotechnology Series, Plenum Publishing Corp., New York]
• Imukin^® ; cloned in Escherichia coli; source : Boehringer Ingelheim, Austria
Indications :
• chronic granulomatous disease (CGD)
• phase III trials for renal cell carcinoma
• adjuvant for HBsAg^ref
• phase III clinical trials to enhance tumour antigen presentation and cytotoxicity (systemic or local route)^ref
Side effects : major depression, influenza-like illness (ILI), insomnia, dysthyroidism.
• interleukins : the suffix -kin is used in naming interleukin-type substances except for interleukin 3 (IL-3) which was classified as a pleiotropic colony-stimulating factor and assigned the "plestim" stem (eg, daniplestim).  The "kin" nomenclature series was divided into subgroups with an adjuvant stem representing the numerical class of the interleukin followed by the kin   suffix.
• IL-1 (-nakin) :
• IL-1a (-onakin)
• pitonakin
• IL-1b (-benakin) :
• betaleukin
• mobenakin
• IL-1ra : anakinra (Kineret^®) 100 mg/day s.c. for rheumatoid arthritis (RA) (2-12 weeks of latency). It reduces tumour invasiveness and alleviates tumour-mediated suppression^ref
• IL-2 (-leukin) (systemic local) is currently used in phase III clinical trials to enhance NK cell and CD8⁺ T-cell immunity (systemic or local route)^{ref1, ref2, ref3, ref4} but can have both positive and negative effects on T cells depending on their stage of differentiation. IL-2 treatment during ...
• expansion phase is detrimental to the survival of rapidly dividing effector T cells
• during the death phase is highly beneficial, resulting in increased proliferation and survival of virus-specific T cells
IL-2 treatment also increases proliferation of resting memory T cells in mice that controlled LCMV infection. Virus-specific T cells in chronically infected mice also responded to IL-2 resulting in decreased viral burden.
• aldesleukin / des-Ala-1-Ser-125-hIL-2 (Proleukin^®, source : Chiron Corp, USA; Leuferon^®; source : Immunex and Roche) (nonglycosylated) used in the treatment of metastatic renal cell carcinoma and metastatic malignant melanoma. Side effects : systemic capillary leak syndrome (SCLS) (65%; due to permeability-enhancing peptide (PEP), i.e. amino acids 22-58: a point mutation at amino acid 38 completely blocks the vasopermeability effect but does not affect cytokine activity), thyroiditis and eosinophilia. Pre-treatment with tumour-targeting antibody-PEP fusion proteins is being developed as a strategy to enhance drug delivery to tumours, such that higher effective doses of chemotherapy can be targeted to tumours without additional systemic side effects.

Premedication :
• high dose, bolus (600,000 units/kg/dose) :
• acetaminophen 650 mg PO prior to each dose q8h
• NSAID (indomethacin 25 mg PO prior to each dose q8h or naproxen 500 mg PO BID during therapy)
• H2-receptor antagonist (cimetidine 300 mg PO/IV at HS or famotidine 20 mg PO/IV at HS or ranitidine 150 mg PO or 50 mg IV at HS)
• low dose, outpatient SC or continuous infusion : acetaminophen 650 mg PO prior to each dose or q4h PRN^ref
• celmoleukin (Celeuk^®, source : Takeda) for angiosarcoma CNS
• teceleukin (nonglycosylated) (Bioleukin^®; source : Biogen)
In patients with renal cancer, the expression of carbonic anhydrase IX predicts the responsiveness to immunotherapy with IL-2^ref, and the expression of B7-H1