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HOW WE DO IT

How to Initiate and Monitor Infusional

Lidocaine for Severe and/or Neuropathic Pain

Rebecca Ferrini, MD, MPH, CMD, and Judith A. Paice, PhD, RN

Dr. Ferrini is Medical Director of Edgemoor Hospital, a long-term, 24-hour skilled nursing care facility operated by the County of San Diego in Santee, California.

Dr. Paice is Director of the Cancer Pain Program, Division of Hematology-Oncology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.

Case Report

The patient, a 51-year-old woman diagnosed with primitive neuroectodermal tumour (peripheral neuroendothelioma) 4 years prior, presented with severe (10/10) unrelenting neuropathic pain due to T6-T8 spinal-cord compression. Increasing doses of intravenous (IV) morphine up to 50 mg/h with frequent 25-mg boluses of morphine provided inadequate relief. Adjuvant analgesics, including gabapentin, baclofen, amitriptyline, clonidine, and clonazepam,provided little relief or caused significant side effects.

Because of the significant pain and lack of response to standard therapies for neuropathic pain, the decision was made to begin a trial of parenteral lidocaine. Treatment with 100 mg of lidocaine IV (approximately 1.5 mg/kg) over 20 minutes produced a rapid decrease in pain intensity over the course of the infusion. Because the trial was successful, a lidocaine infusion was

evere, intractable cancer pain is often due to neuropathic pain syndromes. Neuropathic pain can develop when nerves are injured, compressed, infiltrated, or affected by toxins, as commonly occurs in malignancies, as well as in HIV, diabetes, and other comorbidities common in people with cancer. Although opioids and adjuvant analgesics can be effective in most of these patients, a few individuals will continue to experience unmanageable pain. Novel techniques, such as parenteral lidocaine administration, are beginning to be used in the management of severe neuropathic pain.

Pathophysiology of Neuropathic Pain

To understand the rationale for using parenteral lidocaine, one must appreciate the underlying mechanism of neuropathic pain syndromes. However, because neuropathic pain syndromes represent a diverse group of conditions, one single mechanism cannot explain the underlying pathology. Changes can occur within the peripheral, central, and autonomic nervous system, and multiple

continued at 100 mg/h. Attempts to reduce the lidocaine infusion rate resulted in increased pain.

As this was a new therapy,we attempted a variety of delivery strategies. Continuous subcutaneous, continuous IV, IV bolus only, or a combination of continuous and bolus lidocaine were tried. The patient reported highest satisfaction with a continuous IV infusion accompanied by bolus doses as needed. As her pain was now better controlled, she was discharged home with hospice care after more than 3 months’ hospitalization.

Ongoing clinical monitoring and frequent dosage adjustments continued in the home setting. On average, adequate pain control was maintained with a lidocaine infusion rate of 10– 15 mg/h with a 25-mg bolus of lidocaine every 5 minutes for pain exacerbations. Four months after discharge, she died suddenly after development of superior vena cava syndrome [1].

mechanisms are likely involved. Within the peripheral nervous system, changes include abnormal nociceptor (small fibre neurons transmitting noxious stimuli) sensitization and ectopic impulse generation, leading to spontaneous discharge [2, 3]. The neuron becomes more sensitive to any stimulation, resulting in spontaneous pain and hyperalgesia (normally mild painful stimuli, such as a pin prick, are perceived as extremely painful).

Another hypothesized peripheral mechanism includes the development of ephaptic conduction between sensory neurons, where electrical currents in one neuron excite impulse activity in nearby neurons. Furthermore, neuropeptides, such as the cytokine tumour necrosis factor-α, are released in response to inflammation. These cytokines are believed to generate spontaneous ectopic activation of nociceptors [4]. Since conduction within neurons is mediated in part by changes in ion concentrations across the membrane, agents that block Na+ channels, such as the local anesthetics, are often used to relieve pain [5].

Sodium channel blocking agents, including systemic local anesthetics such as lidocaine, have long been used to treat acute pain and, more recently, chronic pain [6–9]. At subanesthetic doses, lidocaine blocks neuronal function in active or depolarized neurons without interfering with the normal function of other sensory or motor neurons [10]. Historically, outside of its use for procedural pain, parenteral lidocaine has been used as a “challenge” to elucidate whether the patient has neuropathic pain and to ascertain whether adjuvant therapy using oral analogs of lidocaine, such as mexiletine, might be effective. Several open label trials report the benefit of short-term intravenous (IV) lidocaine infusions, lasting 45 minutes to 1 hour, in a variety of neuropathic pain states, including postherpetic and diabetic neuropathy [9, 11, 12]. Anecdotal reports suggest that some patients obtain sustained relief, although many patients report that the pain returns hours or days after the infusion is discontinued.

Based upon these experiences, and the prevalence of severe neuropathic pain in our hospice, we explored the prolonged use of IV or subcutaneous (SC) lidocaine infusions to treat both neuropathic and mixed (neuropathic and nociceptive) pain syndromes.

Initial Experience

While working at an inpatient hospice in 1996, one of us (R.F.) began treating patients suffering from severe neuropathic pain with parenteral lidocaine infusions. At first, we regarded lidocaine as too dangerous for use except by anesthesiologists. Therefore, we investigated lidocaine therapy only in the most difficult-to-treat pain states, restricting its use to only those patients who were closest to death and who might be willing to accept the risk of this “unconventional and possibly dangerous therapy” (as we explained it). However, as our team developed more experience, we came to see lidocaine’s effectiveness, both in controlling patients’ pain and improving their quality of life. Furthermore, despite our fears, we observed little toxicity as an effect of this drug. We have found parenteral lidocaine to be effective in those with chronic neuropathic pain, particularly when it was associated with malignancy, as well as for severe pain of other aetiologies. We have now treated over 100 patients using this technique, some for weeks or months, and have identified advantages to this therapy, as well as characterized those patients who might benefit most from it.

 

Advantages of Lidocaine Therapy

Lidocaine is inexpensive and effective. Adverse effects of sedation, confusion, nausea, and constipation that accompany the use of opioids and other analgesics, tend to occur less frequently with lidocaine therapy. The side-effect profile of parenteral lidocaine delivered by infusion is predictable and has a wide safety margin [4]. Thanks to its short half-life, the symptoms of lidocaine toxicity are transient and easily reversible by lowering the infusion rate.

 

Who Might Benefit From Lidocaine

Infusion Therapy?

Parenteral lidocaine has been reported to be effective in small studies of various neuropathic pain conditions, including diabetic neuropathy, postoperative pain, post-herpetic neuralgia, centrally mediated pain, headache, and malignant nerve infiltration [13–20]. Based upon the experience of R.F. with more than 100 patients, many or all of whom whereas receiving opioids, infusional lidocaine is effective when treating visceral or central pain. Parenteral lidocaine may also be useful when opioids are ineffective or causing unacceptable adverse effects.

PRE-INFUSION ASSESSMENT

To determine whether the patient is a candidate for parenteral lidocaine infusion, a thorough pain assessment is critical. Patients should undergo complete pain history, quantitative pain assessment, and physical examination. Prior adjuvant therapy and allergies to “caine” anesthetics must be elicited. The presence of heart failure or liver disease, which would increase the toxicity of lidocaine, must be ascertained. A complete medication history is essential, as adjuvant therapies and other, less-invasive modalities are warranted prior to beginning parenteral lidocaine.

LIDOCAINE CHALLENGE

The purpose of a lidocaine challenge is to assess whether an individual patient’s pain is responsive to lidocaine and whether the patient can tolerate the medication. The dosage for testing purposes infusional Lidocaine generally 1–3 mg/kg (100 mg is often used) administered IV in a concentration of 8 mg/mL over 20–30 minutes. During the bolus infusion, careful clinical observations of vital signs and pain intensity are conducted at least every 15 minutes. If SC administration is preferred, the initial loading dose is administered over a longer period (30 minutes to 1 hour), and response is generally delayed. If SC infusion is elected, lidocaine is easily concentrated at 40 mg/mL, allowing a 2–3 cc initial dose and hourly infusion rate of 2–3 cc/h. If ineffective, the lidocaine challenge is discontinued and other pain relief modalities must be selected. If effective, an infusion is started.

Lidocaine Infusions

If the lidocaine challenge is effective or partially effective, the patient is started on a continuous infusion, either SC or IV, at 0.5–2 mg/kg per hour, using the lowest possible dose that controls the pain (Table 1). Although lidocaine is generally given as a continuous infusion for pain, we have also tried a patient-controlled analgesia (PCA) format in which the patient could self-administer bolus doses in some cases of intermittent, severe pain.

Lidocaine infusions may reduce pain dramatically or subtly. 

Table 1

When Lidocaine Challenge Works, What Next?

OVER THE NEXT 72 HOURS:

Gradually titrate downward to try to determine the lowest possible effective dose of lidocaine.

Monitor for any signs of toxicity, particularly after dosage increases.

Reduce opioids rapidly if patient demonstrates signs/symptoms of toxicity (particularly sedation).

If pain is exclusively intermittent, initiate a trial of bolus administration.

If the patient did not receive an adequate trial of adjuvant analgesics, sequentially try adjuvant therapy and titrate the dose upward until analgesia or adverse effects occur.

Discuss signs and symptoms of possible toxicity with patients and families.

Assess the competency of the caregiving situation if unable to wean the patient off lidocaine and he or she wishes to return home.

If lidocaine infusion continues to be indicated:

Consider invasive therapies, such as epidural nerve blocks.

Consider home infusion.

 patients will report dramatic stepwise “erasing” of their pain. In other cases, however, patients might say the pain is still severe (rating it a “10” on a scale of 0 to 10) but more “bearable.” Another indication that lidocaine is effective is an improvement in the patient’s functional status (eg, a patient who could not walk due to pain begins to walk) or a reduction in opioid use. Or patients may say, “I don’t feel it working,” but when the rate of infusion is reduced, the pain returns and they notice its previous effectiveness.

TITRATING LIDOCAINE INFUSIONS

As with any therapy, the ideal is to use the lowest effective dose of medication to treat the patient. The usual method of establishing the lowest effective dose is to reduce the dose of lidocaine gradually until pain returns. Doses above 2 mg/kg per hour are rarely indicated. This experience with parenteral lidocaine mirrors that of Wallace and colleagues [8], who reported a lidocaine dose-response curve for pain relief characterized by a clearly defined breakpoint in dosage, below which pain persisted and at or above which pain was dramatically reduced. Although doses may be reduced among those with hepatic or cardiac disease, these conditions are not contraindications in the case of severe neuropathic pain.

TOXICITY

Lidocaine infusions to manage pain are generally in the range of 1–2 mg/kg per hour. At this rate, blood levels are often less than 3 µg/mL and toxicity rarely develops. If blood levels increase, the side effects are sequential, relatively predictable, and easily reversed by stopping or slowing the infusion [4]. At blood levels of 4–6 µg/mL, patients may complain of lightheadedness, numbness around the tongue or mouth, and/or dizziness. They may note a metallic taste in their mouths or experience an increase in blood pressure. The infusion should be slowed or stopped if any one of these events occurs. Although we initially drew blood to measure plasma levels of lidocaine when using this drug for analgesia, this level of monitoring does not seem to be necessary in a palliative care population, nor do most patients want venipuncture.

Plasma concentrations of lidocaine rarely, if ever, exceed these levels when infusions are used for pain. To provide a reference for lidocaine effects at higher plasma levels, at approximately 8 µg/mL, patients can experience visual or auditory disturbances, dissociation, muscle twitching, and decreased blood pressure. At 12 µg/mL, convulsions may be noted; at 16 µg/mL, coma may ensue, and at levels above 20 µg/mL respiratory arrest and cardiovascular collapse can occur. Thus, at the doses used to provide pain relief, parenteral lidocaine infusions are safe.

Other toxicities include local redness or erythema at the SC infusion site. Changing the site every few days can obviate the local irritation.

Titrating Opioids With Lidocaine

Many patients whom we have treated with lidocaine infusions were receiving high doses of parenteral or oral opioids concomitantly. Lidocaine infusions can reduce pain and the need for opioids dramatically. In fact, if opioid dosages are not reduced when pain reduction is achieved through a lidocaine infusion, opioid side effects may develop or worsen.

For example, a previously well-tolerated opioid dose may lead to significant sedation when pain is relieved by infusing lidocaine. Interestingly, we have never seen any sign of opioid withdrawal, despite rapid discontinuation of even high-dose opioid therapy (eg, a reduction from 500 µg/h of SC fentanyl to no opioid use over 24 hours or 90 mg/h of IV hydromorphone titrated to 1–2 mg/h in less than 24 hours).

Adjuvant Therapies

In an ideal world, oral adjuvant therapies would already have been tried prior to instituting a parenteral lidocaine infusion, but some patients may present with severe neuropathic pain without ever having had an adjuvant analgesic. Most adjuvant analgesics must be titrated gradually, delaying pain relief. Ideally, parenteral lidocaine is a time-limited strategy for rapidly treating severe neuropathic pain. Once pain is under control, adjuvant therapy can be instituted and titrated so that the pain can be managed more conveniently, without the need for catheters or infusion pumps.

However, despite a wide variety of adjuvant agents, including antidepressants, anticonvulsants, corticosteroids, and antiarrhythmics, very little information exists regarding which therapies might be most effective in those patients who have responded favourably to lidocaine infusions. The majority of the patients we treated with parenteral lidocaine therapy were successfully transferred to

PATIENT INFORMATION SHEET

Lidocaine Infusion

Lidocaine

Your doctor has prescribed lidocaine to treat your pain. Lidocaine is a local anesthetic similar to the anesthetic dentists use to numb your tooth when you get a filling. It seems to work by quieting nerves, which are firing when they shouldn’t be, thereby reducing your pain.

Lidocaine belongs to an entirely different family from morphine and can be extremely effective at reducing certain kinds of pain. Lidocaine is administered either intravenously (in the vein) or subcutaneously (under the skin) by a portable pump. The pump delivers this medication as a continuous infusion, delivering the same amount every hour for 24 hours a day. In some cases, your pump may allow you to receive extra doses, called bolus doses, which you can give to yourself if the pain returns.

Side Effects of Lidocaine

Lidocaine is a relatively safe drug when given in low doses. However, even at low doses, certain side effects can occur. The most serious side effect is an allergic reaction to the medication, which can produce sudden, severe difficulty in breathing. The allergic reaction also can increase the chances of having an irregular heartbeat, which, in rare cases, can lead to sudden death. Although allergic reactions to lidocaine are serious, they are fortunately rare.

The most common side effects you might experience are usually related to having too much of the drug in your body. When this happens, you may experience numbness around your mouth, dizziness, or even a sense of being drunk, perhaps with slurring of speech.

You also may experience hallucinations, muscle twitches, or even a sense of being detached from your body. Though these side effects go away very quickly, once the infusion is stopped or lowered and blood levels of lidocaine drop, they should prompt a call to your nurse.

In rare cases, lidocaine can produce seizures, usually when the dose being given is too high. In these cases, the infusion should be stopped, the nurse called, and seizure medication given.

Sometimes, you may experience problems in the area where the lidocaine enters the body. If the medication is given under the skin, you and the nurse should check for redness, soreness, or hardening of the site. These signs indicate that the site should be changed. In general, the site should be changed every 3 days. However, if redness develops, the site of entry may have to be changed more frequently.

FROM THE JOURNAL OF SUPPORTIVE ONCOLOGY

Ferrini Paice

Table 2

Protocol for Home Infusion

Determine whether to use:

Subcutaneous or intravenous administration.

Bolus doses only, continuous infusions, or a combination of both.

Patient must have a stable caregiver situation, with 24-hour supervision by a competent adult.

Home Infusion of Lidocaine

If the patient is unable to taper off the lidocaine, refuses or is not a candidate for more invasive therapies, and requires continuous infusion at home for ongoing pain relief and, moreover, strongly desires discharge, home infusion may be considered (Table 2). Lidocaine infusions may be administered

Patient must consent to being visited by a registered nurse 2–7 times a week. at home via an ambulatory pump identical to those

Patients should understand that any redness or induration at the site of subcutaneous injection indicates a need to switch to a different site (abdominal and thigh sites are preferable).

Patient should agree to frequent adjustments of lidocaine dosage in an attempt to determine the minimum dose at which patient is comfortable.

Patient/caregiver should have the ability to clearly describe signs and symptoms of lidocaine toxicity and show ability to turn off the pump.

Patient/caregiver should be provided with a lidocaine patient information sheet.

used for opioid infusions in a PCA setting. Because they are compatible, lidocaine may be used together with opioid infusions. Another advantage is that lidocaine is inexpensive, with a 24-hour supply costing less than $5.

Lessons Learned

Consider providing benzodiazepine in home for sublingual or subcutaneous administration in the event of seizures.

oral agents, most commonly gabapentin. Because

Infusional few data exist, the clinician must use a trial-and error approach, sequentially introducing different

Lidocaine

adjuvant agents and titrating each one until an analgesic or adverse effect occurs. If an adjuvant drug is found to be effective, the lidocaine infusion is gradually reduced and discontinued, if possible. If these attempts fail, patients may be maintained for weeks to months on infusional lidocaine without any adverse effects.

Lidocaine infusions, used over the short or long term, have become an indispensable part of the armamentarium for treating intractable severe pain, particularly neuropathic pain. Regardless of the setting in which lidocaine will be used, the interdisciplinary team must work together to educate themselves about this approach and develop policies and systems for providing this technique in a safe and timely manner. Finally, this modality deserves further study in the hospice and palliative care setting to determine the appropriate dose, schedule, route, and indications for lidocaine infusions to improve comfort at the end of life.

References

Ferrini RL. Infusional lidocaine for terminal

ly ill patients with intractable pain continued at home. Palliat Med 2000;3: 93–201.

Serra J, Ochoa J, Campero M. Human stud

ies of nociceptors in neuropathic pain. In: Hans-son PT, Fields HL, Hill RG, Marchettini P, eds. Neu

ropathic Pain: Pathophysiology and Treatment, Progress in Pain Research and Management. Vol

21. Seattle, Wash: IASP Press; 2001:63–83.

Baron R. Peripheral neuropathic pain: from mechanisms to symptoms. Clin J Pain 2000;16: S12–S20.

Mao J, Chen LL. Systemic lidocaine for neu

ropathic pain relief. Pain 2000;87:7–17.

5.Tanelian DL, Brose WG.Neuropathic pain can be relieved by drugs that are use-dependent sodium channel blockers: lidocaine,carbamazepine and mexiletine. Anesthesiology 1991;74:949–

951.

Dejgard A, Petersen P, Kastrup J: Mexiletine for treatment of chronic painful diabetic neurop

athy. Lancet 1988;1:9–11.

Bach FW, Jensen TS, Kastrup J, et al:The effect of intravenous lidocaine on nociceptive process

ing in diabetic neuropathy. Pain 1990;40:29–34.

Wallace MS,Dyck JB,Rossi SS,Yaksh TL.Com

puter-controlled lidocaine infusion for the eval

uation of neuropathic pain after peripheral nerve injury. Pain 1996;66:69–77.

Rowbotham MC, Reisner-Keller L, Fields HL. Both intravenous lidocaine and morphine reduce the pain of post-herpetic neuralgia. Neurology 1991;41:1024–1028.

Tanelian DL, Victory RA. Sodium channel-blocking agents: their use in neuropathic pain conditions. Pain Forum 1995;4:75–80.

Galer BS, Miller KV, Rowbotham MC. Re

sponse to intravenous lidocaine infusion differs based on clinical diagnosis and site of nervous system injury. Neurology 1993; 43:1233–1235.

Ferrante FM, Paggioli J, Cherukuri S, et al. The analgesic response to intravenous lidocaine in the treatment of neuropathic pain. Anesth Analg 1996;82:91–97.

Marchettini P, Lacerenza M, Marangoni C, et al. Lidocaine test in neuralgia. Pain 1992;48: 377–382.

Edmondson EA, Simpson Jr RK, Stubler DK, Beric A. Systemic lidocaine therapy for post-stroke pain. South Med J 1993;86:1093–1096.

Brose WG, Cousins MJ. Subcutaneous lidocaine for treatment of neuropathic cancer pain. Pain 1991;45:145–148.

Shwager HA, Floyd RA, Ivey JR, et al. Phar

macodynamic modeling of pain response with chronic subcutaneous high concentration lidocaine in the treatment of sympathetically mediated pain. In: Proceedings of the 14th An

nual Scientific Meeting of the American Pain So

ciety; November 1995; Los Angeles, Calif.

Linchitz RM, Raheb JC. Subcutaneous in

fusion of lidocaine provides effective pain relief for CRPS patients. Clin J Pain 1999;15:67–72.

Baranowski AP, De Courcey J, Bonelo E. A trial of intravenous lidocaine on the pain and al

lodynia of post-herpetic neuralgia. J Pain Symp

tom Manage 1999;17:429–433.

Wu CL, Tella P, Staats PS, et al. Analgesic effects of intravenous lidocaine and morphine on postamputation pain: a randomized, double-blind, active placebo-controlled cross-over trial. Anesthesiology 2002;96:841–848.

Hand PJ, Stark RJ. Intravenous lignocaine infusions for severe chronic daily headache. Med J Aust 2000;174:157–159.

www.SupportiveOncology.net THE JOURNAL OF SUPPORTIVE ONCOLOGY

Correspondence to: Rebecca Ferrini, MD MPH, CMD (Certified Medical Director), Medical Director, Edgemoor Hospital, County of San Diego, 9065 Edgemoor Drive, Santee, CA 92071; telephone: (619) 956-2852; e-mail: rebecca.ferrini @sdcounty.ca.gov.

J Support Oncol 2004;2:90–94 © 2004 BioLink Communications

www.SupportiveOncology.net THE JOURNAL OF SUPPORTIVE ONCOLOGY

Lidocaine & other anesthetics

Lidocaine: 

Clinical Pharmacology

CLINICAL PHARMACOLOGY

Mechanism of action: Lidocaine stabilizes the neuronal membrane by inhibiting the ionic fluxes required for the initiation and conduction of impulses, thereby effecting local anesthetic action.

Hemodynamics: Excessive blood levels may cause changes in cardiac output, total peripheral resistance, and mean arterial pressure. With central neural blockade these changes may be attributable to block of autonomic fibers, a direct depressant effect of the local anesthetic agent on various components of the cardiovascular system and/or the beta-adrenergic receptor stimulating action of epinephrine when present. The net effect is normally a modest hypotension when the recommended dosages are not exceeded.

Pharmacokinetics and metabolism: Information derived from diverse formulations, concentrations and usages reveals that lidocaine is completely absorbed following parenteral administration, its rate of absorption depending, for example, upon various factors such as the site of administration and the presence or absence of a vasoconstrictor agent. Except for intravascular administration, the highest blood levels are obtained following intercostal nerve block and the lowest after subcutaneous administration.

The plasma binding of lidocaine is dependent on drug concentration, and the fraction bound decreases with increasing concentration. At concentrations of 1 to 4 mcg of free base per mL, 60 to 80 percent of lidocaine is protein bound. Binding is also dependent on the plasma concentration of the alpha-1-acid glycoprotein.

Lidocaine crosses the blood-brain and placental barriers, presumably by passive diffusion.

Lidocaine is metabolized rapidly by the liver, and metabolites and unchanged drug are excreted by the kidneys. Biotransformation includes oxidative N-dealkylation, ring hydroxylation, cleavage of the amide linkage, and conjugation. N-dealkylation, a major pathway of biotransformation, yields the metabolites monoethylglycinexylidide and glycinexylidide. The pharmacological/toxicological actions of these metabolites are similar to, but less potent than, those of lidocaine. Approximately 90% of lidocaine administered is excreted in the form of various metabolites, and less than 10% is excreted unchanged. The primary metabolite in urine is a conjugate of 4-hydroxy-2, 6-dimethylaniline.

The elimination half-life of lidocaine following an intravenous bolus injection is typically 1.5 to 2.0 hours. Because of the rapid rate at which lidocaine is metabolized, any condition that affects liver function may alter lidocaine kinetics. The half-life may be prolonged two-fold or more in patients with liver dysfunction. Renal dysfunction does not affect lidocaine kinetics but may increase the accumulation of metabolites.

Factors such as acidosis and the use of CNS stimulants and depressants affect the CNS levels of lidocaine required to produce overt systemic effects. Objective adverse manifestations become increasingly apparent with increasing venous plasma levels above 6.0 mcg free base per mL. In the rhesus monkey arterial blood levels of 18-21 mcg/mL have been shown to be threshold for convulsive activity.

Indications and Usage

Lidocaine Hydrochloride Injection, USP is indicated for production of local or regional anesthesia by infiltration techniques such as percutaneous injection and intravenous regional anesthesia by peripheral nerve block techniques such as brachial plexus and intercostal and by central neural techniques such as lumbar and caudal epidural blocks, when the accepted procedures for these techniques as described in standard textbooks are observed.

Contraindications

Lidocaine is contraindicated in patients with a known history of hypersensitivity to local anesthetics of the amide type.

Warnings

LIDOCAINE HYDROCHLORIDE INJECTION, FOR INFILTRATION AND NERVE BLOCK, SHOULD BE EMPLOYED ONLY BY CLINICIANS WHO ARE WELL VERSED IN DIAGNOSIS AND MANAGEMENT OF DOSE-RELATED TOXICITY AND OTHER ACUTE EMERGENCIES THAT MIGHT ARISE FROM THE BLOCK TO BE EMPLOYED AND THEN ONLY AFTER ENSURING THE IMMEDIATE AVAILABILITY OF OXYGEN, OTHER RESUSCITATIVE DRUGS, CARDIOPULMONARY EQUIPMENT, AND THE PERSONNEL NEEDED FOR PROPER MANAGEMENT OF TOXIC REACTIONS AND RELATED EMERGENCIES (See also ADVERSE REACTIONS and PRECAUTIONS). DELAY IN PROPER MANAGEMENT OF DOSE-RELATED TOXICITY, UNDERVENTILATION FROM ANY CAUSE AND/OR ALTERED SENSITIVITY MAY LEAD TO THE DEVELOPMENT OF ACIDOSIS, CARDIAC ARREST AND, POSSIBLY, DEATH.

Intra-articular infusions of local anesthetics following arthroscopic and other surgical procedures is an unapproved use, and there have been post-marketing reports of chondrolysis in patients receiving such infusions. The majority of reported cases of chondrolysis have involved the shoulder joint; cases of gleno-humeral chondrolysis have been described in pediatric and adult patients following intra-articular infusions of local anesthetics with and without epinephrine for periods of 48 to 72 hours. There is insufficient information to determine whether shorter infusion periods are not associated with these findings. The time of onset of symptoms, such as joint pain, stiffness and loss of motion can be variable, but may begin as early as the 2nd month after surgery. Currently, there is no effective treatment for chondrolysis; patients who experienced chondrolysis have required additional diagnostic and therapeutic procedures and some required arthroplasty or shoulder replacement.

To avoid intravascular injection, aspiration should be performed before the local anesthetic solution is injected. The needle must be repositioned until no return of blood can be elicited by aspiration. Note, however, that the absence of blood in the syringe does not guarantee that intravascular injection has been avoided.

Local anesthetic solutions containing antimicrobial preservatives (e.g., methylparaben) should not be used for epidural or spinal anesthesia because the safety of these agents has not been established with regard to intrathecal injection, either intentional or accidental.

 

Ketamine 

KETALAR® (ketamine as hydrochloride) has been studied in over 12,000 operative and diagnostic procedures involving over 10,000 patients from 105 separate studies. During the course of these studies, KETALAR® was administered as the sole agent, as induction for other general anaesthetic agents, or to supplement low potency agents. In these studies, the anaesthesia was rated either “excellent” or “good” by the anaesthetist and the surgeon at 90% and 93% respectively. In a second method of evaluation, the anaesthesia was rated “adequate” in at least 90% and “inadequate” in 10% or less of procedures. Specific areas of application have included the following:

  1. debridement, painful dressings and skin grafting in burn patients as well as other superficial surgical procedures;
  2. neurodiagnostic procedures such as pneumoencephalograms, ventriculograms, myelograms and lumbar punctures;
  3. diagnostic and operative procedures of the eye, ear, nose and mouth including dental extractions;
  4. diagnostic and operative procedures of the pharynx, larynx or bronchial tree;

Note: muscle relaxants with proper attention to respiration, may be required (see

WARNINGS AND PRECAUTIONS)

  1. sigmoidoscopy and minor surgery of the anus and rectum and circumcision;
  2. extraperitoneal procedures used in gynaecology, such as dilation and curettage;
  3. orthopaedic procedures such as closed reductions, manipulations, femoral pinning, amputations and biopsies;
  4. as an anaesthetic in poor-risk patients with depression of vital functions;
  5. in procedures where the intramuscular route of administration is preferred;
  6. in cardiac catheterisation procedures. 

 

Ketamine is rapidly absorbed following parenteral administration. Peak plasma levels averaged 0.75μg/ml and CSF levels were about 0.2μg/ml one hour after dosing.1 The plasma half-life is in the range of 2 to 4 hours.2,3,4 After IM administration (absorption half-life 2-17 minutes) it is up to 93 % bioavailable.1

Distribution

Ketamine (as hydrochloride) is rapidly and extensively distributed throughout the body into highly perfused tissues including the brain. 3,4 Mean volume of distribution is reported to range from approximately 1 to 3 L/kg, and the distribution half-life is approximately 7 to 11 minutes. Ketamine (as hydrochloride) is approximately 20-50% bound to plasma proteins.6 Ketamine is likely to be excreted in breast milk, but this is unlikely to be clinically relevant. The drug crosses the placenta in induction doses but in amounts that have no adverse effects on the neonate5 (see Use in Pregnancy and Use in Lactation).

Metabolism6

Ketamine undergoes extensive hepatic metabolism. The biotranformation includes N- dealkylation to norketamine (metabolite I), hydroxylation of the cyclohexone ring (metabolites III and IV), conjugation with glucuronic acid and dehydration of the hydroxylated metabolites to form the cyclohexene derivative (metabolite II). Norketamine (metabolite I) has about 1/6 of the potency of ketamine and is formed at concentrations in the plasma similar to those of the parent compound.

Elimination

After intravenous bolus administration, ketamine shows a bi- or triexponential pattern of elimination. The alpha phase lasts about 45 minutes with a half-life of 10 to 15 minutes. This first phase, which represents the anaesthetic action of ketamine, is terminated by redistribution from the CNS to peripheral tissues and hepatic biotransformation to an active metabolite. The beta phase half-life is about 2.5 hours.2,3,4 About 90% of ketamine is excreted in the urine, mostly as metabolites, with only about 2 to 4 % as the unchanged drug. Approximately 5% is recovered in the faeces.7 The renal clearance of ketamine hydrochloride is 15 ± 5 mL/min/kg.8

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