Ghai Essential Pediatrics8th

Contraindications Relative contraindications to perito­ neal dialysis include recent abdominal and/or cardio­ thoracic surgery, diaphragmaticperitoneal-pleural fistula, fecal or fungal peritonitis and abdominal wall cellulitis.

Procedure Access for peritoneal dialysis can be achieved by inserting a rigid catheter (Fig. 28.9A) or a single cuff soft Tenckhoff catheter at the bedside (Fig. 28.9B). The doublecuffTenckhoff catheter, used for chronicperitoneal dialysis is placed in the operating room by a surgeon. A rigidacute PD catheter is easily available, inexpensiveand relatively simple to insert. However, the risks of peritonitis are high, particularly if used for more than 48 hr.

The abdomen is cleansed with chlorhexidine and beta­ dineanddraped. Followingadministrationofsedationand local anesthesia, an 18-22 gauge cannula is inserted below the umbilicus in the midline or lateral to the rectus abdo­ minus muscle at two-thirds the distance between the umbilicusandtheanteriorsuperioriliac spine (Fig. 28.9C). About 20-30 ml/kg of peritoneal dialysis fluid is infused till the flanks appear full.The cannula is removed and the stiffcatheterisinserted usingthetrocar. Oncea'giveaway' sensation is felt, dialysis fluid flows freely back into the catheter lumen.Thecatheteris inserted carefully avoiding

Common Medical Procedures -

injury to viscus by the trocar and guiding the tip of the catheter into the left iliac fossa.The trocar is removed and thecatheterattached toa three-wayconnection to the peri­ tonealdialysisfluidandthedrainbag.Onceeasyinflowand outflow areconfirmed, the catheterissecuredwithapurse­ string suture and manual cycles of dialysis are initiated.

The soft single cuff catheter is inserted using an intro­ ducer kitusing themodifiedSeldinger technique. A tunnel is created in the soft tissue so that the exit site is awayfrom the entry point into the peritoneum and the cuff protects from bacterial migration.This catheter is associated with lower risk of peritonitis particularly if used with an auto­ mated cyclerdevice (Fig. 28.9D). Itcanbecappedwhen not in use, allows ease of nursing, and can be used for several weeks (Fig. 28.9E).

Prescription Acute PD can be performedintermittently or continuously depending upon the desired amount of fluid and solute removal, and either manually by nurses or via an automated device. About 20-30 ml/kg is infused over 5 min,keptintheabdomenfor20-40min,andthendrained out. Ultrafiltration occurs due to the osmotic gradient created by the glucose in the fluid.The standard acute PD prescription includes the following components: lengthof

the session, dialysate composition, exchange volume, inflowandoutflow (drain) periods, dwelltime, numberof exchanges and additives such as heparin (for blood clots) or additional dextrose (to create more ultrafiltration). Ultrafiltration should not exceed 5-10% of body weight over 24-48 hr. The prescription is modified every 6-12 hr based on clinical evaluation and laboratory parameters. Acute manual PDrequiresconstantsupervision to ensure accurate inflow, dwell and drain times and the mainte­ nance of a record of exchange and drain volumes and net ultrafiltration. By comparison, the use of the automated cycler reduces need for constant supervision and record maintenance and decreases the number of manual inter­ ruptions and risk of peritonitis.

Complications AcutePDmaybeassociatedwithcompli­ cations, some of which are serious. Abdominal pain or discomfortmayoccurduetoabdominaldistension,impro­ perpositionofthecatheterorperitonitis. Mildhemorrhage isfrequentduringcatheterplacement,particularlywithrigid acute catheters. Leakage around the PD catheter site is common is managed by reducing the exchange volume or placinga suture at theexit site. Inadequatedrainage is due toimproperplacementofthecathetertipordecreasedbowel motility. Bowelperforationsisrarebutmaybeobservedwith theplacementof stiff catheters. Rarecomplications include atelectasis and pleural effusion. Metabolic complications include hyperglycemia, hypokalemia, protein losses and hypernatremia. Theincidenceofperitonitisisdecreasedby maintaining sterile precautions during the placement of catheters,preventingcontaminationduringexchangesand use of a cyclerdevice.

Suggested Reading

Korbet, SM. Acute Peritoneal Dialysis Prescription. In: Handbook of Dialysis, 4th edn, Daugirdas, JT, Blake, PG, Ing, TS (Eds), Lippincott Williams and Wilkins, Philadelphia; 2007:p.382

Passadakis P, Oreopoulos D. Peritoneal dialysis in acute renalfailure. Int J Artif Organs 2003;26:265

or infections involving the bone marrow (kala-azar, tuberculosis).

Sites The iliac crest is the most commonly used site. The sternum is not preferred in children because of associated pain and the risk of injuring underlying vital structures. Marrow may be aspirated from the proximal tibia medial to the tibial tuberosity in infants (<1-yr-old). This site is preferredin infantssincebiopsyfromtheiliacsiteinyoung childrenisdifficultastheiliaccrest issmallandcarries risk of injuring pelvic viscera.

Equipment Varioustypesofbonemarrowbiopsyneedles are available (Figs 28.lOAand B). TheJamshidi needle and its modifications are used widely because of their light weight, sharpbevelledendthatallowseasycoringofbone, ataperingendthatfacilitatesrecoveryofmarrowspecimen and suitability for both aspiration and biopsy.

Procedure The child should be fasting for 3-4 hr before the procedure. The child is positioned prone with face turnedto a sideandthepelvis stabilized by folding a sheet below it. If tibia is to be aspirated, the leg is slightly flexed atthekneejoint.Sedationwithintravenousmidazolamand ketamineisadministeredduringcontinuousmonitoringof vital signs and oxygen saturation. Atropine is used to counteract the secretions associated with use of ketamine.

The site is cleaned with chlorhexidine and betadine to include the lumbar spine, iliac crests and posterior iliac spines (or for the tibial site, the entire leg up to the distal halfofthigh)anddraped. Theposteriorsuperioriliacspine is located by tracing the iliac crest backwards to its most prominent and elevated point. About 2 ml of 1% lidocaine is injected subcutaneously into the periosteum. The bone marrow needle is held firmly in the dominant hand with the index finger placed over the needle to act as a guard. Theneedleisadvancedperpendicularlyintotheidentified area with twisting motion till bone is felt. On advancing further, a 'give way' is felt that indicates that the needle is

Bone Marrow Aspiration and Biopsy

A special bone marrow needle is introduced into the bone marrowspace, andasampleaspirated foranalysis. A mar­ row biopsyistakentoascertainthecellularity,architecture of the marrow.

Indications Bone marrow aspiration and biopsy are indicated in presence of pancytopenia, bicytopenia, unex­ plainedthrombocytopeniaor leukocytosis in order to rule out significant pathology such as lymphoreticular malignancy (acute lymphoblastic or myelogenous leuke­ mia, Hodgkin or non-Hodgkin lymphoma, chronic mye­ loidleukemia,myelodysplasia,myelofibrosis);hypoplastic or aplastic anemia; megaloblastic anemia; sideroblastic anemia; Langerhans cell histiocytosis; hemophagocytosis syndrome; suspected metastasis (retinoblastoma, neuro­ blastoma); infiltrative storage diseases (Gaucher disease)

AB

Figs 28.1 OA and B: Needles for bone marrowaspiration and biopsy.

(A) Jamshidi needles; (B) Vim Silverman needle

in the bone marrow. The stylet is removed and a 20 ml syringe attached. The piston is pulled to create negative pressureandaspirateslowlyaround0.5mlofmarrow.The syringe is disconnected and the marrow placed on slides. To make a touch preparation, the marrow is spread onthe slide byplacing another glass slide soas to smear the mar­ row gently. Additional slides are prepared similar to a peripheral smear, using another glass slide at 30° angle to spread the marrow in a tongue shaped projection on the slide.

Toperformmarrowbiopsy,thestyletisreplacedandthe needle withdrawn slightly. The needle is advanced through anothersiteinthe bone.Oncetheneedleislodged inthebone,the stylet isremoved andtheneedle advanced in rotatory motion through the marrow space. The needle is withdrawn and biopsy specimen placed in a vial con­ tainingformalin.Oncetheneedleisremovedlocalpressure is applied to allow bleeding to stop. Drapes are removed, the skin is cleaned and pressure bandage applied.

Aspirationfrom the tibia isperformed in a similar man­ ner. The preferred site is medial to the tibial tubercle, one inch below the joint line to avoid the growth plate. The needle isintroduced gently with a twisting motion similar to thatdescribed above. The bone cortex isthinner andthe marrowspaceisreachedmorequicklythanwiththepelvic site. Obtaining a biopsy is often difficult as the marrow is more spongy.

Complications Bleeding and pain at the aspiration site are common. Bone injury with fractures of iliac bone and subcutaneousinfections or osteomyelitis are rare.

Liver Biopsy

Indications Liverbiopsyisusedtoevaluatehepatichisto­ logyinorderto: (i)diagnoseparenchymalliverdisease(e.g. neonatal hepatitis, suspected metabolic liver disease); (ii) understand the cause of persistently abnormal liver tests; (iii)determinetheetiologyoffocalordiffuseabnormalities onimagingstudies; (iv)assesstheprognosisofknownliver disease(e.g.extrahepaticbiliaryatresia,autoimmunehepa­ titis, chronic viral hepatitis); (v) determine response to therapeutic interventions; (vi) develop a treatment plan basedonhistology;and(vii)monitoreffects ofhepatotoxic drugs. Analysis of the biopsy specimen may include evaluation of histology, metal content, enzymatic assays and cultures for viral, bacterial, or fungal pathogen.

Contraindications Absolute contraindications include coagulopathy,assuggestedbylowplateletcount(<60.000/ µl)orprolongedprothrombintime(intemationalnormalized ratio>1.5), and an inabilitytoremain still (with or without sedation). Relative contraindications include anemia, peritonitis, markedascites,high-gradebiliaryobstruction, and a subphrenic or right pleural infection or effusion.

Procedure The biopsy may be performed percuta­ neously at bedside with or without ultrasound guidance.

Common Medical Procedures -

Anultrasound guided biopsy carries lower risk ofcompli­ cations and allows visualization of the liver and anytarget lesions. Uncommonly, the biopsy is performed using the transjugular route, laparoscopically or by wedge resection during laparotomy. Transjugular venous biopsy is preferred in patientswith severe coagulopathy.

The child should be fasting for 4-6 hr. An intravenous line is secured and the child made to lie supine. The abdo­ minal girth is measured at the umbilicus to allow subse­ quent comparisons. The lower border of liver is localized by palpation or percussion, and its position on the mid­ clavicular line marked.

Duringcontinuousmonitoring of vital signs sedation is administered with (ketamine and midazolam). The site is cleaned and draped as described previously. The site of biopsy ischosenbased on theliverspan. If theliveris pal­ pable,asubcostalapproach maybeused.However, aright lateral transthoracic approach is most common, in which the needle is inserted in the tenth intercostal space in the midaxillary line, after confirming liver dullness. Local anesthesiaisadministered.Thebiopsyisusuallyperformed usingaspring-loadedsemiautomaticbiopsygun(Fig. 28.11) ofsize18 (infants) or 16 (children)gauge.Thegunisloaded and its needle inserted through the marked intercostal site justabovetheborderofthelowerrib, soastoavoidinjuring the neurovascular bundle running along the lower border of ribs. The needle is inserted carefully along a horizontal planetoadepthat whicha'giveway' sensationisfeltupon ruptureofthelivercapsule.Thetipoftheneedleshouldrest just beyond the capsule and should move well with respiration. The gun is fired and the needle withdrawn quickly.Thesampleistransferredtovials,e.g.formalinfor

histopathology.

I

Fig. 28.11: Semiautomated gun for biopsy of liver and kidney

The biopsy site is sealed with tincture iodine and pres­ sure dressing applied to prevent bleeding. The child is monitored over the next 6-8 hr fortachycardia,tachypnea, hypotensionandincreaseinabdominal girth andexcessive pain, which may suggest internal bleeding.

Complications Major complications such as intra-abdo­ minal hemorrhage, biliary peritonitis, hepatic laceration, hemothorax, hemobilia, pneumothorax, gallbladder or intestinal perforation and iatrogenic arteriovenous fistula are none.

Renal Biopsy

Indications Examination of the renal histology is useful in a significantproportion of patients with acuteor chronic renal diseases. Usual indications include: (i) acute glo­ merulonephritis wherecourse is atypical for poststrepto­ coccal glomerulonephritis(presence of fever, rash or joint pain; lack of serologic evidence of streptococcal infection; normalcomplementC3;delayed resolutionoffeatures)and/ or rapidly progressive glomerulonephritis is present (suggestedbyelevatedcreatinine,anuria,needfordialysis); (ii)nephroticsyndromewithonsetbelow1 yrorinlateadole­ scence;documentedsteroidresistance; presenceofpersistent hematuria, stage II hypertension, elevated levels of serum creatinine or low complement C3; likely secondary cause (infection with hepatitis B, C or HIV, collagen vascular diseases, amyloidosis, tuberculosis)and for evaluationfor calcineurininhibitorassociated nephrotoxicity;(iii)suspec­ ted glomerular gross or microscopic hematuria persisting beyond12-18months(2+ormoreproteinuria,redcellcasts, dysmorphic red cells, and/or azotemia);(iv) unexplained proteinuriainnephroticrange(> 1000mg/m2/day)without lowserumalbuminoredemaorinnon-nephroticrange(100-- 1000mg/m2 per day) along with hematuria;(v) acute renal failure of unidentified etiology, particularly if lasting over 2-3 weeks to identify significant treatable etiology (e.g. crescentic glomerulonephritis, acute interstitial nephritis) ortoassesstheprognosis(extentoftubularorcorticalnecro­ sis);(vi)unexplainedchronickidneydiseasestageIII ormore; (vii) following renal transplantationfordetectingallograft rejection, acute tubular necrosis or drug toxicity; and(viii) suspectedrenalinvolvementinHenoch-Schonleinpurpura, systemiclupus erythematosus ormicroscopicpolyarteritis.

Relative contraindications These include uncontrolled highbloodpressure,coagulopathy(e.g. thrombocytopenia <75,000U/µl,prolonged prothrombin timewithINR>1.5, uremia, use of NSAIDs or warfarin in previous 5-7 days, heparin during last 6-8 hr), solitary kidney and active pyelonephritis. The use of IV desmopressin(DOAVP 0.3 mg/kg30 minprior)ornasalDOAVP(2-4mg/kg2hrbefore theprocedure) reduces the risk of hematuriapostbiopsyin patients with azotemia or prolonged bleeding time.

Procedure Thepatient shouldbefasting4-6hrprior; clear liquidsarealloweduntil2hrbeforethebiopsy. AnIVaccess is established to administer anesthesia with ketamine and midazolam. The patient lies prone, with support under the lower chest and epigastrium. The patient's vital signs are closely monitored during the procedure.

The biopsy is performed using a semiautomatic biopsy gun of 16 or 18 gauge, usually under real-time ultrasono­ graphicguidance.Thesiteiscleanedanddraped.Thelower pole of the kidney is located at the midaxillary line either byultrasoundguidanceorusingaprobingneedle(1Yzinch, 23 gauge; or 9 cm 20 gauge spinal needle) inserted at the renal angle (below the twelfth rib, lateral to the sacro­ spinalis muscle) to a depth where the needle moves well with respiration,indicating entry into the renal pole. Dur­ ing nonguided biopsy, the depth of the needle is marked whileremovingit andthesiteofentryismarked.Lidocaine is injected locally. A small nick is given at the biopsy site with a surgical blade. The needle of the biopsy gun is inserted to a depth such that the needle tip is visible just under the renal capsule on ultrasound; alternatively the needle is inserted to the depth indicated by the probing needleusedforlocalizingthe kidney.Oneto three cores of renal tissue are obtained for processing for light micro­ scopy(in 10% formalin or paraformaldehyde), immuno­ fluorescence(Michel's medium) and electronmicroscopy (glutaraldehyde).

Vital signs are monitored for at least 6-8 hr. At least three urine voids should be inspectedfor gross hematuria. The child is discharged after overnight observation. Contact sports, cycling or lifting of heavy objects should be avoided for 1 week.

Complications Thesemayincludeadverseeffectsrelated to sedation (hypoxia, respiratory depression, vomiting), gross hematuria, perinephric hematoma and intra-abdo­ minal bleeding with hypotension.

Suggested Reading

Uppot RU, Harisinghani MG, Gervais DA. Imaging-guided percutaneous renal biopsy: Rationale and approach. AM J Roentgenol 2010;194:1443-9

INTRODUCTJON

Medications play an important role in protecting, main­ taining and restoring health. Irrational and indiscriminate use may lead to toxicity and adverse reactions. It is better to use medications with which the physician is familiar. The expected benefits and side effects should always be kept in mind when prescribing. The principles of rational drug therapy can be summarized as:

i.There should be a genuine indication for use of the medication.

ii.A minimum number of appropriate, familiar and inexpensive agents of good quality should be used.

iii.The drugs should preferably be prescribed by their generic name.

iv.The dosage should be optimum to achieve the desired benefits.

v.It is desirable to administer medication, as far as possible, through oral route.

vi.Adverse drug reactions should be anticipated,

monitored and appropriately managed.

True synergism is rare; an exception is cotrimoxazole (trimethoprim and sulfamethoxazole). Combination of antibiotics may be necessary when the causative agent is notknown.Multidrugtherapyisindicatedto preventresis­ tance to individual drugs, during longterm management oftuberculosisandleprosyand toreducetoxicityofindivi­ dual drugs. Bactericidal drugs act best when the organism isactivelymultiplyingand shouldideallynotbecombined with bacteriostatic drugs.

Developmental and genetic factors affect the metabo­ lism of drugs and thereby the response. Doses of drugs need to be modulated according to the individual respon­ ses. The dosages may vary in specific disease, e.g. pneu­ monia, meningitis, bacterial endocarditis and pyogenic arthritis.

The doses given below are approximate doses used in common practice. The reader is advised to consult the prescribing information for each medication.

Anu Thukral, Ashok K. Deorari

Abbreviations. d day;g gram;GI gastrointestinal;hr hour; IM intramuscular;IV intravenous;kg kilogram;m2 square meterbodysurface;mg milligram;µg microgram,PO per oral;PR per rectal;SC subcutaneous;T topical;wt weight; yr age in years

ANALGESICS, ANTIPYRErtCS, NONSTEROJDAL ANTI­

INFLAMMATORV DRUGS (NSAJDs)

Non-narcotic Analgesics

Aspirin. Acute rheumatic fever: 90-120 mg/kg/day PO q 4 hr. Rheumatoid arthritis: 65-130 mg/kg/day PO q 4-6 hr;antipyreticdose: 30-60 mg/kg/dayPO q 4-6 hr; Kawasaki disease 80-100 mg/kg/day PO q 4-6 hr till afebrile or for 2 weeks followed by 3-5 mg/kg/day PO OD for 6-8 weeks. Side effects: Hypersensitivity, hypopro­ thrombinemia. Due to an epidemiologic association of salicylate usewith Reyeencephalopathy,theuse of aspirin for fever of undetermined origin in children is not advi­ sable. Salicylates should be avoided empty stomach.

Paracetamol. 40-60 mg/kg/dayPO q 4-6 hr or 15 mg/kg/ dose PO 4-6 hr; 5 mg/kg IM. Side effects: Skin rashes, hepatotoxicity, and occasionally, renal damage.

Ibuprofen. Antipyretic/analgesic dose 20-30 mg/kg/ day q 6-8 hr PO or 10 mg/kg/dose q 4-6 hr; maximum dose 40-60 mg/kg/day; juvenile rheumatoid arthritis: 30-70 mg/kg/day q 4-6 hr; closure of ductus arteriosus in neonates: 10 mg/kg followed by 5 mg/kg every 24 hr for 2 days. Side effects: Nausea, vomiting, rashes.

Naproxen. Juvenile rheumatoid arthritis: 10-20 mg/kg/ day q 12 hr; analgesia 5-7 mg/kg/dose q 8-12 hr. Side effects: Nausea, vomiting, rashes.

Diclofenac sodium. 1-3 mg/kg/day PO q 8 hr. Side effects:

Gastric bleeding, ulcer.

Mefenamic acid. 25 mg/kg/day PO q 6-8 hr. Antipyretic dose: 5-8 mg/kg/dose. Side effects: Gastric bleeding, rash, seizures.

Indomethacin. 3 mg/kg/day PO q 8 hr. Dose for ductal closure depends on the age of the neonate (Table 29.1). Side effects: Oliguria, hypoglycemia, platelet dysfunction.

Tramadol. 1-2 mg/kg q 4-6 hr up to maximum of 400 mg/ day; avoid below 14 yr of age. Side effect: Seizures, renal and hepatic dysfunction.

Table 29.1: Dose of indomethacin dose (mg/kg) in neonates

Narcotic Analgesics (Opioids)

Fentanyl. 0.5--5µg/kg/doseq1-4hrIV,maybeadministered as a continuous infusion 1-5 µg/kg/hr. Potent narcotic analgesic; 0.1mgdosepossessesanalgesicactivity;equiva­ lent to 10 mg of morphine. Side effects: Rapid infusion may cause chest wall rigidity; respiratory distress and respira­ tory arrest.

Codeine. For pain: 3 mg/kg/day PO q 4 hr; antitussive: 0.2 mg/kg/dose q 4 hr (1-1.5 mg/kg/day). Side effects: Respiratory distress, increased intracranial pressure. Contraindicated in patients with ventilator failure, obs­ tructive airway disease.

Pethidine. 1-2 mg/kg/dose IM or IV. Side effects: Seizures.

Morphine. 0.1-0.2 mg/kg/dose q 4 hr (max. 15 mg) IV, IM, SC.Forcontinuousinfusioninneonates0.01-0.02mg/ kg/hr; infants and children 0.01-0.04 mg/kg/hr. Caution: Keep naloxone (0.01 mg/kg IV) ready as antidote in case ofrespiratorydepression. Side effects: Respiratorydistress, increased intracranialpressure, seizures. Contraindicated in patients with ventilatoryfailure andobstructive airway disease.

ANTIARRHYTHMICS

Adenosine. 0.1 mg/kg/dose rapid IV (over 1-3 sec); if no response in 1-2 min, give 0.2 mg/kg bolusthroughathree way. To ensure that the drug reaches the circulation, administer directly into a vein with athree way stopcock with 5-10 ml of saline flush ready to push immediately. Maximum single dose 0.25 mg/kg or 12 mg. Side effects: Transient chest pain, dyspnea, flushing, bronchospasm.

Atropine sulfate. 0.01mg/kg/dose SC orIV.Minimum dose 0.1 mg, maximum single dose 0.5 mg; adolescent 1 mg. The dose can be repeated after 2 hr (max 4-6 times a day). Organophosphorus poisoning: 0.02-0.05 mg/kg every 10-20 min until atropine effect, then every 1-4 hr for at least 24 hr. Side effects: Dry mouth, blurred vision, tachycardia, urinary retention, constipation, dizziness, hallucinations and ventilatory restlessness.

Bretylium. 5-20 mg/kg/day q 8 hr PO or 5-10 mg/kg IM or IV. Repeated 1-2 hr if arrhythmia persists and subse­ quently given every 6-8 hr for 3 to 5 days.

Lidocaine hydrochloride. 1 mg/kg/dose IV (maximum 100 mg). May repeat after 5-10 min. Continuous IV infusion 0.02-0.05mg/kg/min. Maximumdose5 mg/kg/ day. Side effects: Hypotension, seizures and asystole, respiratory arrest.

Phenytoin sodium. For arrhythmia: Loading 1.25 mg/kg IV over 3 min and repeat every 5-10 min to a maximum total doseof15mg/kgoruntilarrhythmiarevertsorhypotension develops; maintenance 5-10 mg/kg/day q 12 hr PO. For status epilepticus: Loading 15-20 mg/kg IV, do not exceed 1-3 mg/kg/min. Maintain with 5-8 mg/kg/day PO or IV q 12-24 hr. Side effects: Gum hypertrophy, hirsutism, hypersensitivity, megaloblastic anemia, osteomalacia and vestibulocerebellar syndrome.

Procainamide. 2mg/kg/dose IV followedby 0.5 mg/kg/hr by constant IV infusion. PO dose 50 mg/kg/day q 3-4 hr. Side effects: Thrombocytopenia, Coombs' positive hemolytic anemia, lupus like syndrome. Contraindication: Heart block and myasthenia gravis.

Propranolol. 0.01-0.25 mg/kg/dose; given as IV bolus over 10 min. Maximum dose 1 mg in infants; 3 mg in children. May repeat in 15 min and then every 4-8 hr. PO dose 0.5- 1 mg/kg/day q 6 hr. Side effects:Life-threatening increase in pulmonary resistance, fatigue and bradycardia.

Quinidine sulfate. Test dose 2 mg/kg PO followed by 30 mg/kg/day PO q 6 hr. Side effects: Thrombocytopenia, anemia, tinnitus, hypotension, blood dyscrasias. Contra­ indicated in heart block and congestive heart failure.

Verapamil. 2-4 mg/kg/day q 8 hr PO, 0.1-0.2 mg/kg IV over 2 min in infants and 0.1-0.3 mg/kg IV over 2 min in children. Contraindication: Cardiogenic shock, AV block, age below 2 yr.

AGENTS FOR MYASTHENIA

Edrophonium chloride. Initial dose: 0.04 mg/kg dose IV, IM (maximum 1 mg for <30 kg). If no response after 1 min, may give 0.16 mg/kg/dose for a total of 0.2 mg/kg (total maximumdoseis 5mgfor <30kg).Sideeffects:Arrhythmias and bronchospasm.

Neostigmine bromide. Neonate: Initially, 0.05-0.1 mg IM or SC route, then PO 1 mg 30 min before feed. Children: 1-3 mg/kg/day PO q 4-6 hr or 0.01-0.04mg/kg IV, IM or SC q 2-3 hr. Begin with lower dose and increase gradually till symptoms disappear. Use with atropine for nondepolarizing neuromuscular blocking agents. Side effects: Cholinergic crisis, bronchospasm, respiratory depression, hypotension, seizures, salivation, vomiting, diarrhea and lacrimation. Contraindicated in urinary and intestinal obstruction.

Pyridostigmine. For infants of myasthenic mothers: 0.05- 0.15mg/kg/dose q 4 -6hr IV or IM;then 7mg/kg/dayPO q 4 -6 hr.Start at lower dose and increase gradually.Side effects: Cholinergic effect (same as neostigmine).

Physostigmine. 0.0 0 1 -0.0 3 mg/kg/dose IM, SC, IV.Repeat q 15-20 min to desired effect or maximum dose of 20 mg. Side effects: Cholinergic effects (same as neostigmine).

ANTIBIOTICS

Penicillins

Penicillin may cause hypersensitivity reactions in about 1 % of individuals.Acute symptoms include urticaria, angioneurotic edema , anaphylactic shock, asthma, laryngeal edema and hypotension.Delayed reactions are fixed drug eruption, serum sickness, hemolytic anemia and recurrent arthralgia.Sodium and potassium content of penicillin G is 0.3 mEq and 1.7 mEq per million units, respectively.Large doses may cause seizures (Table 29.2).

Rational Drug Therapy -

Cephalosporins

Approximately 1 0 % patients with penicillin hypersensi­ tivityshowallergytocephalosporin;fatalanaphylaxismay occur.Oral cephalosporins cause gastrointestinal symp­ toms such as loss of appetite, nausea ,vomiting and diarrhea (Table 29.3).

Aminoglycosides

Aminoglycosides cause variable degrees of auditory and vestibular toxicity and reversible kidney dysfunction. Rashesanddrugfeversoccurin about5%patients.Dosage shouldbereducedandintervalbetweendosagesincreased in patients with impaired renal function.Administration of aminoglycoside dose once in 24 hr and as infusion reducestheriskof renalandauditorytoxicity (Table 29.4).

Tetracyclines

Tetracyclines are deposited in growing teeth and bones; doxycyclinedoes not bind as avidly.If used, between the

Third generation cephalosporins (high CSF concentrations; widely used in meningitis)

ages of2 months and8yr, both deciduous and permanent teethmayshowirreversiblestaining, hypoplasiaofenamel and caries. Prolonged use may lead to stunting. Tetra­ cyclines are not recommended in children below 8 yr of age (Table29.5).

Chlo ramph enicol

It may cause idiosyncratic bone marrow depression and hypersensitivity reactions: like fever, rash, angioneurotic edema and GI disturbances. Neonates, especially prema­ ture, may show grey baby syndrome with abdominal distension, vomiting, refusal to suck, dyspnea, cyanosis, peripheral circulatory collapse and death (Table29.6).

Table 29.6: Chloramphenicol

Ointment available as 0.5 and 1%

Macrolides

Macrolides may cause diarrhea, nausea, abnormal taste, raised transaminases and cholestatic jaundice. Clari­ thromycinhaslessabdominaldiscomfort;usewithterfena­ dine, astemazole or cisapride may result in arrhythmias. Multiple drug interactions are noted (less with azithro­ mycin)(Table29.7).

Qu inolones

Side effects: GI upset, renalfailure,insomnia,dizziness and seizures;no concernsofarthropathy. Inhibit liverenzymes; elevated levels of theophylline. Rash, photosensitivity, raised transaminases and neutropenia (Table29.8).

Sulfonamides

Side effects. Blood dyscrasias, exfoliative dermatitis, serum sickness and drug fever (Table29.9).

Other antibiotics used commonly are listed in Table 29.10.

Table 29.9. Trimethoprim sulfamethoxazole (Cotrimoxazole)

Enteric fever: Trimethoprim 10; PO Pneumocystis pneumonia: Trimethoprim 20; PO

Prophylaxis

Pneumocystis: Trimethoprim 5 mg/kg alternate day; PO Urinary infections: 1-2; PO

ANTIFUNGAL AGENTS

Amphotericin B. Test dose 0.1 mg/kg IV; then start 0.25 mg/kg/day; increase by 0.25mg/kg daily, until dose of 1 mg/kg/day. Dilute in 5% dextrose, saline; protect fromlight.Totaldoseshouldnotexceed30-35mg/kg over 4-6 weeks. Side effects: Febrile reactions, nephrotoxicity, hypokalemia and blood dyscrasias.

Liposomal Amphotericin B. 3-5 mg/kg/dose once daily; maximum 15 mg/kg/day. Side effects: as above.

Flucytosine. 50-150 mg/kg/day PO q 6 hr. Side effects:

Neutropenia, thrombocytopenia,colitisandhepatotoxicity.

Griseofulvin. 10 mg/kg/day PO q 12 hr; double dose for extensive lesions. Side effects: Urticaria, paresthesia, proteinuria, leukopenia, photosensitivity; multiple drug interactions.

Griseofulvin. Microsize: Children >2 yr: 20-25 mg/kg/day q 8-12 hr. Ultra111icrosize: Children >2 yr: 15 mg/kg/day q 8-12 hr.

Fluconazole. Loading dose 10 mg/kg IV/PO, then main­ tenance 3-6 mg/kg/day q 24 hr. Side effects: Dizziness, skin rash, hepatic dysfw1ction; drug interactions.

Ketoconazole. 3-6 mg/kg/day PO single dose. Side effects:

Abdominal pain, headache, dizziness, somnolence, photophobia, thrombocytopenia, gynecomastiain adoles­ cents and drug interactions.

Itraconazole. 3-5 mg/kg/day (oral thrush); 5-10 mg/kg/ day (histoplasmosis); maximum 400 mg/day.

Prophylaxis in immunocompromised. 2-5 mg/kg/dose q 12-24hr. Sideeffects: Hearing loss, arrhythmia,hepatotoxic; use cautiously in patients with liver disease and cardiac dysfunction.

Miconazole. 20-40 mg/kg/day PO q 8 hr; 2% local cream. Side effects: Pruritis, rash and thrombocytopenia.

Nystatin. 1-2 million units/day q 8 hr PO for diarrhea due to Candida albicans. For mucosa} application: Dissolve 100,000 units nystatin per ml glycerine.

Terbinafine. Not recommended below 2 yr. For .$.20 kg: 62.5 mg q 24 hr; 20-40 kg: 125 mg q 24 hr; >40 kg: 250 mg q 24 hr for 2-6 weeks.

Voriconazole. 6 mg/kg/dose for 2 doses q 12 hr, then 3-4 mg/kg/dose 12 hr; 5-7 mg/kg/dose for invasive aspergillosis, oral: 3-5 mg/kg/dose 12 hr. Side Effects: Blurred vision, photophobia, photosensitivity, hepatic impairment and flu-like symptoms.

Caspofungin. <3 months: 25 mg/m2/dose (max. 50 mg) once daily; older children: 70 mg/m2 on day 1, followed by 50-70 mg/m2 once daily (max. 70 mg). To be used cautiously in patients with liver disease. Side effects: Elevated transaminases, diarrhea, vomiting, flu-like symptoms and rash.

ANTHELMINTHICS

Albendazole. 1-2 yr: 200 mg single dose; >2 yr and adults: 400 mg single dose. Side effects: Anorexia, vomiting. StrongtJloides, taeniasis, H. nana: 400 mg daily for 3 days. Hydatid cyst: 400 mg twice daily for 28 days (3 cycles at 14 days interval). Neurocysticercosis: 15-20 mg/kg/day for 2-3 weeks. Filaria: 400 mg single dose.

Diethylcarbamazine citrate. Filariasis: 6 mg/kg/day q 8 hr for 2 weeks; tropical eosinophilia: 10 mg/kg/day PO q 8 hr for 1 month; Loeffler syndrome: 15 mg/kg single dose for 4 days. Side effects: Gastrointestinal upset and drowsiness.

Ivermectin. Dose200µg/kgPOsingledose. Contraindicated in children <5-yr-old.

Mebendazo/e. 100 mg PO twice daily for 3 days; repeat after two weeks.

Piperazine citrate. Enterobiasis: 50 mg/kg/day for 7 days; ascariasis: 150 mg/kg/PO single dose for 2 days. Side effects: Vomiting, blurred vision, uriticaria. Contrain­ dicated in patients with epilepsy.

Praziquantel. Neurocysticercosis: 50 mg/kg/day q 8 hr PO for 10-14 days. Tapeworms: 10-20 mg/kg single dose. Liver fluke infestation: 75 mg/kg/day q 8 hr for 2 days.

Pyrantel pamoate. 10 mg/kg of pyrantel base, PO single dose with a maximum of 1 g. Repeat after one week.

Thiabendazo/e. 50 mg/kg/day q 12 hr up to a maximum dose of 3 g/day. Duration of therapy for Strongyloides 2 days, intestinal nematodes 2 days, cutaneous larva mig­ rans 2-5 days, visceral larva migrans 5-7 days and trichinosis 2-4 days.

ANTIMALARIALS

Refer to Chapter 10

ANTIPROTOZOAL

Chloroquine. 10 mg/kg/day PO q 8 hr for 14-21 days for extraintestinal amebiasis. Side effects: Nausea, vomiting, itching. IV administration has been reported to cause hypotension, arrhythmias and cardiac depression.

Dehydroemetine dihydrochloride. 1-3 mg/kg/day PO q 8 hr for 10-15 days or 1 mg/kg/day IM for 7-10 days. Side effects: Renal and cardiac toxicity.

DiloxanideJuroate. Luminalamebicinfection,cysts: 20 mg/ kg/day PO q 8 hr for 10 days. Side effects: Nausea and flatulence.

Metronidazole. Giardiasis: 10 mg/kg/day PO q 8 hr for 10 days. Amebiasis: 20 mg/kg/day PO q 8 hr for 21 days or 50 mg/kg/day PO q 8 hr for 7 days. Side effects: Diarrhea, leukopenia and metallic taste.

Pentamidine: Leishmaniasis: 4 mg/kg/day IM or slow IV infusion daily dose for 12 to 15 doses; a second course may be given after 2 weeks. Side effects: Breathlessness, tachycardia, dizziness, fainting, headache and vomiting.

Secnidazole. 30 mg/kg PO single dose. Hepatic amebiasis treatment for 5 days.

Sodium stibogluconate. Cutaneous leishmaniasis: 20 mg/ kg/day IM, IV for 20 days; mucocutaneous leishmaniasis and systemic infection: treat for 30 days. Side effects: Nausea, vomiting, prolonged QT interval.

Tinidazole. 50 mg/kg/day PO for 2-3 days. Side effects: Same as for metronidazole. Giardiasis: 50 mg/kg single dose (see Chapter 10).

Nitazoxanide. 1-4 yr: 100 mg twice a day for 3 days; 4-12 yr: 200 mg twice a day for 3 days.

ANTIVIRAL AGENTS

Antiretroviral drugs. DrugdosesareprovidedinChapter 10.

Acyclovir. HSY encephalitis: 20 mg/kg/dose q 8 hr for 21 days; neonatal herpes simplex: 60 mg/kg/day q 8 hr IV. Herpes simplex: 1500 mg/m2/day IV q 8 hr.

Varicella or varicella zoster: 80 mg/kg/day q 6 hr PO for 5 days (benefit if within 24 hr of onset of rash). Adole­ scents: 800 mg q 6 hr for 7 days. Immunocompromised hosts: 1500 mg/m2/day IV q 8 hr, treated for 7-10 days.

Ribavirin. Respiratory syncytial virus: Ribavarin (6 g) diluted in 300 ml sterilewater; nebulize 12-18hrdailyfor 3-7 days.

Oral. 10 mg/kg/day q 6-8 hr (max dose 150 mg/d <10 yr; 200 mg/d >10 yr). Side effects: Seizures, congestive heart failure, urinary retention and leukopenia.