Keratoconus: an inflammatory disorder?

Keratoconus has been classically defined as a progressive, non-inflammatory condition, which produces a thinning and steepening of the cornea. Its pathophysiological mechanisms have been investigated for a long time. Both genetic and environmental factors have been associated with the disease. Recent studies have shown a significant role of proteolytic enzymes, cytokines, and free radicals; therefore, although keratoconus does not meet all the classic criteria for an inflammatory disease, the lack of inflammation has been questioned. The majority of studies in the tears of patients with keratoconus have found increased levels of interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α), and matrix metalloproteinase (MMP)-9. Eye rubbing, a proven risk factor for keratoconus, has been also shown recently to increase the tear levels of MMP-13, IL-6, and TNF-α. In the tear fluid of patients with ocular rosacea, IL-1α and MMP-9 have been reported to be significantly elevated, and cases of inferior corneal thinning, resembling keratoconus, have been reported. We performed a literature review of published biochemical changes in keratoconus that would support that this could be, at least in part, an inflammatory condition.

Sedimentation patterns caused by scallop dredging in a physically dynamic environment.

Scallop dredging grounds in the Firth of Lorn, western Scotland, are juxtaposed with rocky reef habitats raising concerns that reef communities may be impacted by sediment disturbed by nearby scallop dredging. A particle-tracking model of sediment transport and settling is applied at two scales. In the near-field, a suspension of typical sand/gravel-dominated bed sediment is subjected to a steady current across the dredge track. In the far-field, silt particles, which may persist in suspension for multiple tidal cycles, are tracked in the context of a regional model of tidally-driven flow. The principal sedimentary risk to reef habitats is predicted to come from settling sand particles when dredge tracks approach within tens of metres of a reef. The cumulative effect of dredging at the relatively low intensities recorded in this region is not expected to have a significant long-term impact on suspended silt concentrations and settlement in this highly dispersive environment.

Antisense down regulation of connexin31.1 reduces apoptosis and increases thickness of human and animal corneal epithelia.

The roles of the gap junction protein connexin31.1 (Cx31.1) are poorly understood, especially as the protein appears to form non-functional channels. Cx31.1 specific antisense oligodeoxynucleotides (ODNs) were designed to evaluate its roles in a corneal epithelium model. Expression of Cx31.1 in corneal epithelium extends from the suprabasal layers of polyhedral wing cells through to the flat squamous cells of superficial layers which are shed into the tear film. Deoxyribozymes (Dzs) were tested for cleavage efficacy using in vitro transcribed Cx31.1 mRNA. Cleavage results showed a putative tertiary structure for Cx31.1 mRNA with one region appearing to have a higher potential for antisense targeting. Application of antisense ODNs designed to this region caused Cx31.1 knockdown in rat and human corneal organotypic culture models, leading to a reduction in apoptosis and a thickening of the corneal epithelium (p=0.0045). Cx31.1 appears to play a role in triggering cell death; knocking it down may provide a novel approach for tissue repair and engineering.

Metallic embolism from intravenous injection of elemental mercury in a 27-year-old male for excision of multiple subcutaneous foreign body granuloma under general anesthesia

This is a case of 27-year-old male who sustained multiple metallic embolism from non-accidental self-injection of elemental mercury through the intravenous route. The patient allegedly self-injected at least twenty thermometers' worth of elemental mercury in a span of one year. The patient presented with generalized body fatigue, difficulty in position sense, distal hand weakness, tremors, labile mood, insomnia, and emotional instability. Physical examination showed multiple subcutaneous granulomas in the extremities at the sites of elemental mercury injection. Radiographic studies in the lungs, abdomen and extremities showed multiple dense spherules and pinpoint opacities indicative of metallic mercury embolism. Serum mercury levels were elevated. The patient underwent multiple hemodialysis sessions due to acute renal failure and tubular nephropathy secondary to mercury poisoning. The patient was eventually referred to the anesthesia department for excision of foreign body granulomas. Fentanyl, Propofol, Atracurium and Sevoflurane were used to induce and maintain anesthesia. Intra-operative course was unremarkable. Chelation therapy with DMSA (2,3-dimercaptosuccinic acid) was done postoperatively. Serum mercury was undetectable 20 days after surgery and chelation therapy. There were no postoperative complications. The patient was discharged well after 43 days of admission.

Age-related differences in the normal human cornea: a laser scanning in vivo confocal microscopy study.

AIMS: To quantify and establish baseline normative data for age-related differences in cellular and innervation density in the normal, healthy, human cornea using laser scanning in vivo confocal microscopy. METHODS: Cross-sectional study of 85 normal subjects assessed via corneal topography and laser scanning in vivo confocal microscopy. RESULTS: Mean age was 38+/-16 years (range 18-87 years) and 60% of subjects were female. Anterior keratocyte density declined by 0.9% per year (r = -0.423, p<0.001), posterior keratocyte density declined by 0.3% per year (r = -0.250, p = 0.021) and endothelial cell density declined by 0.5% per year (r = -0.615, p<0.001). Sub-basal nerve fibre density declined by 0.9% per year (r = -0.423, p<0.001). No association was observed between age and basal epithelial cell density, or between age and central corneal thickness, corneal astigmatism or horizontal corneal diameter (p>0.05). No association was observed between subject gender and corneal cell or innervation density. CONCLUSIONS: Using laser scanning in vivo confocal microscopy this study highlights a significant, and relatively linear, reduction in keratocyte and endothelial cell density with increasing subject age. Interestingly, corneal sub-basal nerve fibre density also significantly decreases with increasing age. In vivo laser scanning confocal microscopy provides a safe, non-invasive method for the establishment of normative data and assessment of alterations in human corneal microstructure following surgery or disease processes.

Involvement of corneal nerves in the progression of keratoconus.

Keratoconus is a debilitating corneal thinning disease that principally develops in the second and third decades of life. Our group previously developed a novel approach to studying keratoconus, based on the observation that there is a gradient of damage across the keratoconic cone. We identified a number of cellular characteristics of keratoconus such as discrete incursions of fine cellular processes from the anterior keratocytes in association with localised indentation of the basal epithelium, and increased levels of the lysosomal enzymes Cathepsin B and G in aberrant keratocytes, located beneath compromised regions of Bowman's layer, but also deeper in the stroma. Enzyme activity by these cells seemed to be causing localised structural degradation of the anterior stroma, leading to near-complete destruction of both Bowman's layer and the stroma, often necessitating a full-thickness corneal graft for sight restoration. This current study extends our initial findings by investigating the role of corneal nerves passing between the stroma and epithelium at the sites of early degradative change observed previously, and may be facilitating the keratocyte-epithelial interactions in this disease. Cells in sections of normal and keratoconic human corneas were labelled with the fixable fluorescent viability dye 5-chloromethylfluorescein diacetate, antibodies to alpha-tubulin (nerves), alpha3beta1 integrin, Cathepsin B and G, and the nuclear dye DAPI, and then examined with a confocal microscope. Anterior keratocyte nuclei were seen wrapping around the nerves as they passed through the otherwise acellular Bowman's layer, and as the disease progressed and Bowman's layer degraded, these keratocytes were seen to express higher levels of Cathepsin B and G, and become displaced anteriorly into to the epithelium. Localised nerve thickenings also developed within the epithelium in association with Cathepsin B and G expression, and appeared to be very destructive to the cornea. Insight into the molecular mechanisms of keratoconic disease pathogenesis and progression can be gained from the process of extracellular matrix remodelling known from studies of connective tissues other than the cornea, and wound healing studies in the cornea. Further studies are required to determine how well this model fits the actual molecular basis of the pathogenesis of keratoconus.

Cellular incursion into Bowman's membrane in the peripheral cone of the keratoconic cornea.

Analysis of corneal tissue from normal and keratoconic donors has revealed differences which may represent early signs in the pathogenesis of keratoconus. Peripheral areas of keratoconic tissue obtained from transplant surgery were targeted to ascertain cellular disposition and morphological changes which may be masked within the extensive damage of the central keratoconic cone. Peripheral keratoconic corneae exhibited discrete incursion of fine cellular processes into Bowman's membrane. These processes originated from keratocytes and were often observed in conjunction with a defined indentation from the basal epithelium. Comparison of the lysosomal enzymes cathepsin B and G with constitutively expressed cytoplasmic esterase determined that both cathepsins were elevated within keratocytes of keratoconic tissue compared with normal tissue. Some clusters of keratoconic keratocytes had elevated levels of cathepsin exceeding all others. Cathepsin-rich keratocytes localized with morphologically compromised regions of Bowman's membrane. The presence of cell nests deeper within the stroma indicated that the catabolic changes, which are visible within the acellular Bowman's membrane, are probably also occurring deeper within the stroma, but are masked and not readily detectable.

Microstructural assessment of rare corneal dystrophies using real-time in vivo confocal microscopy.

PURPOSE: To analyse and describe three cases of rare corneal dystrophy and highlight their in vivo microstructural features. METHODS: Subject 1 was diagnosed with a posterior stromal fleck corneal dystrophy Two of her three children were also affected. Subjects 2 and 3 exhibited an almost identical clinical appearance on biomicroscopic examination, such that both clinically were diagnosed as having pre-Descemet's dystrophies. All subjects underwent in vivo confocal microscopy and approximately 300 sequential digital images were obtained and analysed for each cornea. RESULTS: In vivo confocal microscopy of subject 1 demonstrated an abnormal appearance of numerous large ovoid particles, measuring 50-70 microm in diameter in the mid and posterior stroma as well as smaller hyperreflective dot-like intracellular deposits, of less than 1 microm diameter. Despite the near-identical clinical appearance, subjects 2 and 3 could be clearly differentiated by in vivo confocal microscopy. Subject 2 exhibited small, irregular, optically dense particles, mainly in the anterior stroma, whereas subject 3 possessed classical involvement of the stroma immediately adjacent to Descemet's membrane, with numerous regular small, hyperreflective particles. CONCLUSIONS: The ability of in vivo confocal microscopy to localize and accurately measure various elements in different corneal layers may help to resolve whether abnormalities are intra- or extracellular, and aid clearer differentiation of rare corneal disorders.

A trypanosome structure involved in transmitting cytoplasmic information during cell division.

African trypanosomes are protozoan parasites that cause sleeping sickness in humans through a tsetse fly vector. The procyclic form of Trypanosoma brucei has a single, attached flagellum that describes a helical path along the cell from posterior to anterior. During division, a specific flagellum-flagellum connection is elaborated between the new and old flagellum. This connector was present only during cell duplication and was found to be involved in the replication of the helical cell pattern and polarity. This finding implicates the concept of cytotaxis in cell morphogenesis in trypanosomes.

Differential diagnosis of corneal oedema assisted by in vivo confocal microscopy.

The purpose of this study was to demonstrate microstructural differences between clinically similar, but aetiologically different, cases of corneal oedema in four subjects. In vivo confocal microscopy highlighted oedema of the basal epithelium, prominent nerve-keratocyte interactions, and typical 'epithelialization' of the endothelium in a case of iridocorneal endothelial syndrome; however, a similar microstructural appearance was observed in a case of presumed herpetic disciform keratitis. The latter diagnosis was subsequently revised on this basis. Confocal examination of Fuchs' endothelial dystrophy demonstrated oedema of the basal epithelium, prominent wing cells, anterior stromal alterations, fibrosis of Descemet's membrane and a typical 'strawberry' appearance of the endothelium. In contrast, in vivo microstructural examination of bilateral keratoconus with hydrops confirmed oedema mainly involving the epithelium and anterior stroma. In vivo confocal microscopy allows the clinician to observe the living cornea at a microstructural level and to better diagnose and differentiate borderline or unusual cases of corneal oedema.

Assessing the quality of asthma care provided to Medicaid patients enrolled in managed care organizations in Connecticut.

BACKGROUND: Many states have enrolled Medicaid beneficiaries in managed care organizations (MCOs). Few assessments of the quality of asthma care provided by these new programs are available. OBJECTIVE: To describe the quality of care provided to asthmatic Medicaid children enrolled in MCOs. METHODS: For this cross-sectional survey, a chart abstraction tool was developed to evaluate fulfillment of key performance measures chosen from a national guideline for asthma diagnosis and management. These measures were prescription of an inhaled anti-inflammatory medication, accomplishment of patient education, evaluation of exposure to environmental triggers of asthma, and administration of influenza vaccination. From State of Connecticut administrative databases, a random sampling of Medicaid children, ages 5 to 18 years, enrolled in four MCOs was selected. Chart entries from July 1, 1996 to June 30, 1997 were reviewed using the abstraction tool. Accomplishment of performance measures was evaluated for the total sample and for children who were high utilizers of medical services (at least one ED visit or hospitalization during the study period). RESULTS: For 80 high utilizers among 315 children, completion of performance measures was suboptimal: 46% were prescribed inhaled steroids; an action plan was outlined for 43%; evaluation of patient or family tobacco use was documented for 56%; evaluation of the presence of a pet for 43% or mite exposure for 19%; and allergy skin testing or RAST was accomplished for 15%. CONCLUSIONS: This information suggests that opportunities exist to improve the quality of care for these children.

Architecture of the Trypanosoma brucei nucleus during interphase and mitosis.

The structural basis of mitosis, spindle organisation and chromosome segregation, in the unicellular parasite Trypanosoma brucei is poorly understood. Here, using immunocytochemistry, fluorescent in situ hybridisation and electron microscopy, we provide a detailed analysis of mitosis in this parasite. We describe the organisation of the mitotic spindle during different stages of mitosis, the complex ultrastructure of kinetochores and the identification of a potential spindle-organising centre in the mitotic nucleus. We investigate the dynamics of chromosome segregation using telomeric and chromosome-specific probes. We also discuss the problems involved in chromosome segregation in the light of the fact that the T. brucei karyotype has 22 chromosomes in the apparent presence of only eight ultrastructurally defined kinetochores.

Cell-cycle and developmental regulation of TbRAB31 localisation, a GTP-locked Rab protein from Trypanosoma brucei.

Rab proteins are small GTPases that control the direction and timing of vesicle fusion during intracellular trafficking between membraneous compartments. Genome sequencing and EST analysis of Trypanosoma brucei indicates that the trypanosome Rab (TbRAB) gene family, and hence complexity of intracellular transport pathways, is intermediate between Saccharomyces cerevisiae and mammals. TbRAB31 is a constitutively expressed T. brucei Rab protein (formerly Trab7p) and is the product of one of two closely linked TbRAB genes, the other being TbRAB2 (TbRab2p, in: Field H, Ali BRS, Sherwin T, Gull K, Croft SL, Field MC. TbRab2p, a marker for the endoplasmic reticulum of Trypanosoma brucei, localises to the ERGIC in mammalian cells. J Cell Sci 1999; 112:147-156), involved in ER to Golgi transport. TbRAB31 has high homology to members of the Sec4/Ypt1 subfamily of Rab proteins from S. cerevisiae and to Rab13 and Rab11 from higher eukaryotes. Recombinant TbRAB31 binds GTP but, unusually for a Rab protein, has undetectable GTPase activity resulting in a constitutively GTP-bound protein. Antibodies against TbRAB31 recognise a discrete structure located between the kinetoplast and nucleus in interphase procyclic cells; by contrast the structure is morphologically more complex in bloodstream form (BSF) parasites, consisting of at least two foci. TbRAB31 behaviour was also studied during the cell cycle; TbRAB31 always localised to a discrete structure that duplicated very early in mitosis and relocated to daughter cells in a coordinate manner with the basal body and kinetoplast, suggesting the involvement of microtubules. Additional evidence suggests that TbRAB31 localises to the trypanosome Golgi complex. Firstly, the interphase position of TbRAB31 is consistent with a Golgi location. Secondly, the TbRAB31 structure is also recognised by cross-reacting antibodies to mammalian beta-coatomer protein (beta-COP), which localises to the Golgi in mammalian cells. Thirdly, the fluorescent ceramide analogue, BODIPY-TR-ceramide, a reliable marker of the mammalian Golgi apparatus, exhibited overlapping distribution with TbRAB31. The location of BODIPY-TR-ceramide was confirmed at the trypanosome Golgi by histochemistry with diaminobenzidine and electron microscopy.

Does adjunctive midazolam reduce recovery agitation after ketamine sedation for pediatric procedures? A randomized, double-blind, placebo-controlled trial.

STUDY OBJECTIVE: Despite widespread use of adjunctive benzodiazepines during ketamine sedation, their efficacy in reducing recovery agitation in children has never been studied. We wished to characterize the nature and severity of recovery agitation after ketamine sedation in children treated in the emergency department and to determine whether the addition of adjunctive midazolam reduces the magnitude of such recovery agitation. METHODS: The study was a randomized, double-blind, clinical trial of adjunctive midazolam versus placebo during ketamine sedation. We enrolled 104 children aged 12 months to 15 years (median age, 6 years) at a combined university medical center and children's hospital. Subjects received either intravenous midazolam (0.05 mg/kg up to 2 mg) or placebo after intravenous administration of a ketamine loading dose (1.5 mg/kg). Treating physicians and nurses independently noted the presence of crying, hallucinations, and nightmares during recovery and graded recovery agitation by using a 100-mm visual analog scale. Preprocedure agitation and external stimulation during recovery were also graded. The time from ketamine injection until each subject met the recovery criteria was recorded. RESULTS: Fifty-three subjects received midazolam, and 51 received placebo. Potentially confounding variables were similar between the groups. Sedation efficacy, adverse effects, and recovery time were also similar between groups. Interobserver agreement between physician and nurse assessments was substantial. Median physician assessment of recovery agitation was 4 mm (interquartile range, 2 to 19) in the midazolam group and 5 mm (interquartile range, 3 to 14) in the placebo group (difference -1; 95% confidence interval -3 to 2; P =.705). Recovery agitation was moderately correlated with preprocedure agitation (rho=0.486) but not with external stimulation during recovery (rho=0.147). CONCLUSION: Recovery agitation is common but generally of very low magnitude after ketamine sedation in children in the ED. We observed a median physician rating of 5 mm on a 100-mm visual analog scale, a score that we believe to be clinically insignificant. The degree of recovery agitation after ketamine sedation is significantly related to the degree of preprocedure agitation. In this study, concurrent midazolam did not diminish such agitation and had no measurably beneficial effect. Use of adjunctive benzodiazepines in pediatric ketamine sedation appears unnecessary.

An alternate technique to close neurosurgical incisions using octylcyanoacrylate tissue adhesive.

The present authors have applied the use of tissue adhesive octylcyanoacrylate, recently approved by the FDA, in the closure of routine neurosurgical cases. The authors find this to be an excellent substitute for nylon, staples, vicryl or steristrip final layer closure of the surgical incision. This is especially useful in the pediatric neurosurgical practice where young children can be emotionally traumatized by the experience of suture or staple removal. We recommend octylcyanoacrylate closure as a safe, simple, quick, cost-effective method of skin closure that has superior applications in pediatric neurosurgical wound closure when used with proper technique.

Protein transport and flagellum assembly dynamics revealed by analysis of the paralysed trypanosome mutant snl-1.

The paraflagellar rod (PFR) of Trypanosoma brucei is a large, complex, intraflagellar structure that represents an excellent system in which to study flagellum assembly. Molecular ablation of one of its major constituents, the PFRA protein, in the snl-1 mutant causes considerable alteration of the PFR structure, leading to cell paralysis. Mutant trypanosomes sedimented to the bottom of the flask rather than staying in suspension but divided at a rate close to that of wild-type cells. This phenotype was complemented by transformation of snl-1 with a plasmid overexpressing an epitope-tagged copy of the PFRA gene. In the snl-1 mutant, other PFR proteins such as the second major constituent, PFRC, accumulated at the distal tip of the growing flagellum, forming a large dilation or 'blob'. This was not assembled as filaments and was removed by detergent-extraction. Axonemal growth and structure was unmodified in the snl-1 mutant and the blob was present only at the tip of the new flagellum. Strikingly, the blob of unassembled material was shifted towards the base of the flagellum after cell division and was not detectable when the daughter cell started to produce a new flagellum in the next cell cycle. The dynamics of blob formation and regression are likely indicators of anterograde and retrograde transport systems operating in the flagellum. In this respect, the accumulation of unassembled PFR precursors in the flagellum shows interesting similarities with axonemal mutants in other systems, illustrating transport of components of a flagellar structure during both flagellum assembly and maintenance. Observation of PFR components indicate that these are likely to be regulated and modulated throughout the cell cycle.

Genetic dissection of the Leishmania paraflagellar rod, a unique flagellar cytoskeleton structure.

The paraflagellar rod (PFR) is a unique network of cytoskeletal filaments that lies alongside the axoneme in the flagella of most trypanosomatids. While little is known about how two major Leishmania mexicana PFR protein components, PFR1 and PFR2, assemble into this complex structure, previous analysis of PFR2 null mutants demonstrated that the PFR is essential for proper cell motility. The structural roles of PFR1 and PFR2 are now examined through comparison of PFR2 null mutants with new PFR1 null mutant and PFR1/PFR2 double null mutant parasites. Both PFR1 and PFR2 were essential for PFR formation and cell motility. When elimination of one PFR gene prevented assembly of a native PFR structure, the other PFR protein accumulated at the distal flagellar tip. Comparison of PFR substructures remaining in each mutant revealed that: (1) fibers that attach the PFR to the axoneme did not contain PFR1 or PFR2, and assemble in the absence of a PFR. (2) PFR1 was synthesized and transported to the flagella in the absence of PFR2, where it formed a stable association with the axoneme attachment fibers. (3) PFR2 was synthesized and transported to the flagella in the absence of PFR1, though it was not found associated with the axoneme attachment fibers. (4) PFR1 and PFR2 were located throughout the subdomains of the PFR. These data suggest that while PFR filaments contain both PFR1 and PFR2, the PFR is attached to the axoneme by interaction of PFR1 with the axoneme attachment fibers.

Assembly of the paraflagellar rod and the flagellum attachment zone complex during the Trypanosoma brucei cell cycle.

Trypanosomes possess a single flagellum that is attached to their cell body via the flagellum attachment zone (FAZ). The FAZ is composed of two structures: a cytoplasmic filament complex and four microtubules situated next to it. There is a complex transmembrane crosslinking of this FAZ to the paraflagellar rod (PFR) and axoneme within the flagellum. We have partially purified the FAZ complex and have produced monoclonal antibodies both against the FAZ and the paraflagellar rod. The two antibodies against the FAZ (L3B2 and L6B3) recognise the cytoplasmic filament in immunofluorescence and in immunoelectron microscopy. On western blot, they detect a doublet of high molecular weight (M(r) 200,000). Two anti-PFR antibodies (L13D6 and L8C4) recognise the paraflagellar rod in immunofluorescence, but show a difference on Western blot: L13D6 recognises both major PFR proteins, whereas L8C4 is specific for only one of them. Using these new antibodies we have shown that although the growth of both cytoplasmic FAZ filament and external PFR are related, their growth initiates at different time points during the cell cycle and the two structures elongate at distinct rates.

TbRab2p, a marker for the endoplasmic reticulum of Trypanosoma brucei, localises to the ERGIC in mammalian cells.

The Rab family of small GTPases is a subset of the Ras superfamily. Rabs regulate the flux through individual steps of the intracellular membrane trafficking pathway, such as ER-to-Golgi transport, probably by controlling SNARE complex assembly. In Trypanosoma brucei a number of Rab proteins have been isolated by EST analysis; here we characterise one of these, TbRab2p (originally designated Trab1p), which is a member of the Ypt1p subfamily of Rab proteins. Recombinant TbRab2p is capable of hydrolysing GTP and is post-translationally modified in vitro by addition of a geranylgeranyl prenyl group, properties of an authentic Rab GTPase. Antibodies against recombinant TbRab2p show that in trypanosomes TbRab2p is localised primarily to the endoplasmic reticulum (ER) and colocalises with BiP in wild-type trypanosomes. Over expression of TbRab2p in procyclic form T. brucei results in a cell population having a 40-fold increase in TbRab2p expression. In these cells biosynthesis of procyclin, a secretory pathway glycoprotein, is decreased, accompanied by an increase in general protein biosynthesis, suggesting that excess TbRab2p affects ER function. Heterologous expression of TbRab2p in COS cells resulted in targeting to the pre-Golgi transport intermediate (ERGIC), indicating that the targeting information is conserved between mammals and trypanosomes. Clustal and phylogenetic analyses support assignment of TbRab2p as a Rab2 homologue. In addition, over expression of TbRab2p in trypanosomes results in membrane reorganisation and formation of opaque vesicular structures visible by phase contrast microscopy, consistent with accumulation of ER-derived vesicular structures in cells highly overexpressing TbRab2p. Ultrastructural examination by electron microscopy confirmed the presence of a tubulo-vesicular membrane bound compartment in close proximity to the cis-Golgi, probably equivalent to the ERGIC. TbRab2p is therefore a new ER/ERGIC marker for T. brucei.

Intravenous ketamine for pediatric sedation in the emergency department: safety profile with 156 cases.

OBJECTIVES: To determine the safety of i.v. ketamine when administered by emergency physicians (EPs) for pediatric procedures, and to contrast the sedation characteristics of the i.v. and i.m. routes. METHODS: The study was a retrospective consecutive case series of children aged < or =15 years given i.v. ketamine in the EDs of a university medical center and an affiliated county hospital over a 9-year period. A protocol for ketamine was used by treating physicians. Records were reviewed for adverse effects, indication, dosing, adjunctive drugs, inadequate sedation, and time to release. Results were contrasted with previously reported data for the i.m. route. RESULTS: During the study period i.v. ketamine was administered 156 times, primarily for laceration repair and fracture reduction. Transient apnea and respiratory depression occurred in one patient each; both were quickly identified and were without sequelae. Laryngospasm or aspiration was not noted in any children. There were 6 children with emesis and 2 with mild agitation during recovery. The median time from initial dose to ED release was 103 minutes (25th to 75th percentiles 76 to 146 minutes). The i.v. and i.m. routes were comparable in terms of adverse effects, inadequate sedation, and time to release. CONCLUSION: I.v. ketamine can be administered safely by EPs to facilitate pediatric procedures when used in a defined protocol. The sedation characteristics of the i.v. and i.m. routes appear comparable.